Skip to main content

Nitric Oxide and the Vascular Endothelium

  • Chapter

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 176/I))

Abstract

The vascular endothelium synthesises the vasodilator and anti-aggregatory mediator nitric oxide (NO) from L-arginine. This action is catalysed by the action of NO synthases, of which two forms are present in the endothelium. Endothelial (e)NOS is highly regulated, constitutively active and generates NO in response to shear stress and other physiological stimuli. Inducible (i)NOS is expressed in response to immunological stimuli, is transcriptionally regulated and, once activated, generates large amounts of NO that contribute to pathological conditions. The physiological actions of NO include the regulation of vascular tone and blood pressure, prevention of platelet aggregation and inhibition of vascular smooth muscle proliferation. Many of these actions are a result of the activation by NO of the soluble guanylate cyclase and consequent generation of cyclic guanosine monophosphate (cGMP). An additional target of NO is the cytochrome c oxidase, the terminal enzyme in the electron transport chain, which is inhibited by NO in a manner that is reversible and competitive with oxygen. The consequent reduction of cytochrome c oxidase leads to the release of superoxide anion. This may be an NO-regulated cell signalling system which, under certain circumstances, may lead to the formation of the powerful oxidant species, peroxynitrite, that is associated with a variety of vascular diseases.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   259.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Abu Soud HM, Stuehr DJ (1993) Nitric oxide synthases reveal a role for calmodulin in controlling electron transfer. Proc Natl Acad Sci USA 90:10769–10772

    PubMed  CAS  Google Scholar 

  • Adak S, Wang Q, Stuehr DJ (2000) Arginine conversion to nitroxide by tetrahydrobiopterin-free neuronal nitric oxide synthase. J Biol Chem 275:33554–33561

    PubMed  CAS  Google Scholar 

  • Ahn KY, Mohaupt MG, Madsen KM, et al. (1994) In situ hybridization localization of mRNA encoding inducible nitric oxide synthase in rat kidney. Am J Physiol 267:F748–F757

    PubMed  CAS  Google Scholar 

  • Albina JE (1995) On the expression of nitric oxide synthase by human macrophages. Why no NO? J Leukoc Biol 58:643–649

    PubMed  CAS  Google Scholar 

  • Alderton WK, Cooper CE, Knowles RG (2001) Nitric oxide synthases: structure, function and inhibition. Biochem J 357:593–615

    PubMed  CAS  Google Scholar 

  • Alderton WK, Angell AD, Craig C, et al. (2005) GW274150 and GW273629 are potent and highly selective inhibitors of inducible nitric oxide synthase in vitro and in vivo. Br J Pharmacol 145:301–312

    PubMed  CAS  Google Scholar 

  • Aliev G, Bodin P, Burnstock G (1998) Free radical generators cause changes in endothelial and inducible nitric oxide synthases and endothelin-1 immunoreactivity in endothelial cells from hyperlipidemic rabbits. Mol Genet Metab 63:191–197

    PubMed  CAS  Google Scholar 

  • Aoyagi M, Arvai AS, Tainer JA, et al. (2003) Structural basis for endothelial nitric oxide synthase binding to calmodulin. EMBO J 22:766–775

    PubMed  CAS  Google Scholar 

  • Arnet UA, McMillan A, Dinerman JL, et al. (1996) Regulation of endothelial nitric oxide synthase during hypoxia. J Biol Chem 271:15069–15073

    PubMed  CAS  Google Scholar 

  • Asselbergs FW, van der Harst P, Jessurun GAJ, et al. (2005) Clinical impact of vasomotor function assessment and the role of ACE-inhibitors and statins. Vascul Pharmacol 42:125–140

    PubMed  CAS  Google Scholar 

  • Ayajiki K, Kindermann M, Hecker M, et al. (1996) Intracellular pH and tyrosine phosphorylation but not calcium determine shear stress-induced nitric oxide production in native endothelial cells. Circ Res 78:750–758

    PubMed  CAS  Google Scholar 

  • Azadzoi KM, Master TA, Siroky MB (2004) Effect of chronic ischemia on constitutive and inducible nitric oxide synthase expression in erectile tissue. J Androl 25:382–388

    PubMed  CAS  Google Scholar 

  • Azuma H, Ishikawa M, Sekizaki S (1986) Endothelium-dependent inhibition of platelet aggregation. Br J Pharmacol 88:411–415

    PubMed  CAS  Google Scholar 

  • Baek KJ, Thiel BA, Lucas S, et al. (1993) Macrophage nitric oxide synthase subunits. Purification, characterization, and role of prosthetic groups and substrate in regulating their association into a dimeric enzyme. J Biol Chem 268:21120–21129

    PubMed  CAS  Google Scholar 

  • Balligand JL, Kelly RA, Marsden PA, et al. (1993) Control of cardiac muscle cell function by an endogenous nitric oxide signaling system. Proc Natl Acad Sci USA 90:347–351

    PubMed  CAS  Google Scholar 

  • Barbacanne MA, Rami J, Michel JB, et al. (1999) Estradiol increases rat aorta endothelium-derived relaxing factor (EDRF) activity without changes in endothelial NO synthase gene expression: possible role of decreased endothelium-derived superoxide anion production. Cardiovasc Res 41:672–681

    PubMed  CAS  Google Scholar 

  • Barbato JE, Tzeng E (2004) Nitric oxide and arterial disease. J Vasc Surg 40:187–193

    PubMed  Google Scholar 

  • Barouch LA, Harrison RW, Skaf MW, et al. (2002) Nitric oxide regulates the heart by spatial confinement of nitric oxide synthase isoforms. Nature 416:337–339

    PubMed  CAS  Google Scholar 

  • Bates TE, Loesch A, Burnstock G, et al. (1995) Immunocytochemical evidence for a mitochondrially located nitric oxide synthase in brain and liver. Biochem Biophys Res Commun 213:896–900

    PubMed  CAS  Google Scholar 

  • Bauer PM, Fulton D, Boo YC (2003) Compensatory phosphorylation and protein-protein interactions revealed by loss of function and gain of function mutants of multiple serine phosphorylation sites in endothelial nitric oxide synthase. J Biol Chem 278:14841–14849

    PubMed  CAS  Google Scholar 

  • Bauersachs J, Fleming I, Scholz D, et al. (1997) Endothelium-derived hyperpolarizing factor, but not nitric oxide, is reversibly inhibited by brefeldin A. Hypertension 30:1598–1605

    PubMed  CAS  Google Scholar 

  • Beckman JS, Beckman TW, Chen J, et al. (1990) Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci USA 87:1620–1624

    PubMed  CAS  Google Scholar 

  • Beierwaltes WH, Potter DL, Shesely EG (2002) Renal baroreceptor-stimulated renin in the eNOS knockout mouse. Am J Physiol 282:F59–F64

    CAS  Google Scholar 

  • Beltran B, Orsi A, Clementi E, et al. (2000) Oxidative stress and S-nitrosylation of proteins in cells. Br J Pharmacol 129:953–960

    PubMed  CAS  Google Scholar 

  • Benjafield AV, Morris BJ (2000) Association analyses of endothelial nitric oxide synthase gene polymorphisms in essential hypertension. Am J Hypertens 13:994–998

    PubMed  CAS  Google Scholar 

  • Berkels R, Stockklauser K, Rosen P, et al. (1997) Current status of platelet NO synthases. Thromb Res 87:51–55

    PubMed  CAS  Google Scholar 

  • Bernal-Mizrachi C, Gates AC, Weng S, et al. (2005) Vascular respiratory uncoupling increases blood pressure and atherosclerosis. Nature 435:502–506

    PubMed  CAS  Google Scholar 

  • Biffl WL, Moore EE, Moore FA, et al. (1996) Nitric oxide reduces endothelial expression of intercellular adhesion molecule (ICAM)-1. J Surg Res 63:328–332

    PubMed  CAS  Google Scholar 

  • Blatter LA, Wier WG (1994) Nitric oxide decreases [Ca2+]i in vascular smooth muscle by inhibition of the calcium current. Cell Calcium 15:122–131

    PubMed  CAS  Google Scholar 

  • Blot S, Arnal JF, Xu Y, et al. (1994) Spinal cord infarcts during long-term inhibition of nitric oxide synthase in rats. Stroke 25:1666–1673

    PubMed  CAS  Google Scholar 

  • Boger RH, Bode-Boger SM, Szuba A, et al. (1998) Asymmetric dimethylarginine (ADMA): a novel risk factor for endothelial dysfunction: its role in hypercholesterolemia. Circulation 98:1842–1847

    PubMed  CAS  Google Scholar 

  • Bolotina VM, Najibi S, Palacino JJ, et al. (1994) Nitric oxide directly activates calciumdependent potassium channels in vascular smooth muscle. Nature 368:850–853

    PubMed  CAS  Google Scholar 

  • Boo YC, Jo H (2003) Flow-dependent regulation of endothelial nitric oxide synthase: role of protein kinases. Am J Physiol 285:C499–C508

    CAS  Google Scholar 

  • Boo YC, Sorescu G, Boyd N, et al. (2002) Shear stress stimulates phosphorylation of endothelial nitric-oxide synthase at Ser1179 by Akt-independent mechanisms: role of protein kinase A. J Biol Chem 277:3388–3396

    PubMed  CAS  Google Scholar 

  • Boo YC, Sorescu GP, Bauer PM, et al. (2003) Phosphorylation of eNOS at Ser635 stimulates NO production in a Ca2+-independent manner. FASEB J 17:A805

    Google Scholar 

  • Bouloumie A, Schini-Kerth VB, Busse R (1999) Vascular endothelial growth factor upregulates nitric oxide synthase expression in endothelial cells. Cardiovasc Res 41:773–780

    PubMed  CAS  Google Scholar 

  • Boutin JA (1997) Myristoylation. Cell Commun Signal 9:15–35

    CAS  Google Scholar 

  • Bowen R, Haslam RJ (1991) Effects of nitrovasodilators on platelet cyclic nucleotide levels in rabbit blood; role for cyclic AMP in synergistic inhibition of platelet function by SIN-1 and prostaglandin E1. J Cardiovasc Pharmacol 17:424–433

    PubMed  CAS  Google Scholar 

  • Brandes RP, Schmitz-Winnenthal FH, Feletou M, et al. (2000) An endothelium-derived hyperpolarizing factor distinct from NO and prostacyclin is a major endothelium-dependent vasodilator in resistance vessels of wild-type and endothelial NO synthase knockout mice. Proc Natl Acad Sci USA 97:9747–9752

    PubMed  CAS  Google Scholar 

  • Bredt DS, Snyder SH (1990) Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme. Proc Natl Acad Sci USA 87:682–685

    PubMed  CAS  Google Scholar 

  • Bredt DS, Hwang PM, Glatt CE, et al. (1991) Cloned and expressed nitric oxide synthase structurally resembles cytochrome P-450 reductase. Nature 351:714–718

    PubMed  CAS  Google Scholar 

  • Brouet A, Sonveaux P, Dessy C, et al. (2001) Hsp90 and caveolin are key targets for the proangiogenic nitric oxide-mediated effects of statins. Circ Res 89:866–873

    PubMed  CAS  Google Scholar 

  • Brown GC (1999) Nitric oxide and mitochondrial respiration. Biochim Biophys Acta 1411:351–369

    PubMed  CAS  Google Scholar 

  • Brown GC, Cooper CE (1994) Nanomolar concentrations of nitric oxide reversibly inhibit synaptosomal respiration by competing with oxygen at cytochrome oxidase. FEBS Lett 356:295–298

    PubMed  CAS  Google Scholar 

  • Bucci M, Gratton JP, Rudic RD, et al. (2000) In vivo delivery of the caveolin-1 scaffolding domain inhibits nitric oxide synthesis and reduces inflammation. Nat Med 6:1362–1367

    PubMed  CAS  Google Scholar 

  • Busconi L, Michel T (1993) Endothelial nitric oxide synthase: N-terminal myristoylation determines subcellular localization. J Biol Chem 268:8410–8413

    PubMed  CAS  Google Scholar 

  • Busse R, Mulsch A (1990) Calcium-dependent nitric oxide synthesis in endothelial cytosol is mediated by calmodulin. FEBS Lett 265:133–136

    PubMed  CAS  Google Scholar 

  • Buttery LD, Springall DR, Chester AH, et al. (1996) Inducible nitric oxide synthase is present within human atherosclerotic lesions and promotes the formation and activity of peroxynitrite. Lab Invest 75:77–85

    PubMed  CAS  Google Scholar 

  • Cai H, Harrison DG (2000) Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res 87:840–844

    PubMed  CAS  Google Scholar 

  • Cai H, Davis ME, Drummond GR, et al. (2001) Induction of endothelial NO synthase by hydrogen peroxide via a Ca2+/calmodulin-dependent protein kinase II/janus kinase 2-dependent pathway. Arterioscler Thromb Vasc Biol 21:1571–1576

    PubMed  CAS  Google Scholar 

  • Cao S, Yao J, Shah V (2003) The proline-rich domain of dynamin-2 is responsible for dynamin-dependent in vitro potentiation of endothelial nitric oxide synthase activity via selective effects on reductase domain function. J Biol Chem 278:5894–5901

    PubMed  CAS  Google Scholar 

  • Carr A, Frei B (2000) The role of natural antioxidants in preserving the biological activity of endothelium-derived nitric oxide. Free Radic Biol Med 28:1806–1814

    PubMed  CAS  Google Scholar 

  • Caulin-Glaser T, Garcia-Cardena G, Sarrel P, et al. (1997) 17 β-Estradiol regulation of human endothelial cell basal nitric oxide release, independent of cytosolic Ca2+ mobilization. Circ Res 81:885–892

    PubMed  CAS  Google Scholar 

  • Chambliss KL, Shaul PW (2002) Rapid activation of endothelial NO synthase by estrogen: evidence for a steroid receptor fast-action complex (SRFC) in caveolae. Steroids 67:413–419

    PubMed  CAS  Google Scholar 

  • Chance B, Sies B, Boveris A (1979) Hydroperoxide metabolism in mammalian organs. Physiol Rev 59:527–605

    PubMed  CAS  Google Scholar 

  • Charles IG, Palmer RM, Hickery MS, et al. (1993) Cloning, characterization, and expression of a cDNA encoding an inducible nitric oxide synthase from the human chondrocyte. Proc Natl Acad Sci USA 90:11419–11423

    PubMed  CAS  Google Scholar 

  • Chartrain NA, Geller DA, Koty PP, et al. (1994) Molecular cloning, structure and chromosomal localization of the human inducible nitric oxide synthase gene. J Biol Chem 269:6765–6772

    PubMed  CAS  Google Scholar 

  • Chen LY, Mehta JL (1996) Further evidence of the presence of constitutive and inducible nitric oxide synthase isoforms in human platelets. J Cardiovasc Pharmacol 27:154–158

    PubMed  CAS  Google Scholar 

  • Chen ZP, Mitchelhill KI, Michell BJ, et al. (1999) AMP-activated protein kinase phosphorylation of endothelial NO synthase. FEBS Lett 443:285–289

    PubMed  CAS  Google Scholar 

  • Choi YB, Lipton SA (2000) Redox modulation of the NMDA receptor. Cell Mol Life Sci 57:1535–1541

    PubMed  CAS  Google Scholar 

  • Chowdhary S, Townend JN (1999) Role of nitric oxide in the regulation of cardiovascular autonomic control. Clin Sci (Lond) 97:5–17

    PubMed  CAS  Google Scholar 

  • Cieslik K, Abrams CS, Wu KK (2001) Up-regulation of endothelial nitric-oxide synthase promoter by the phosphatidylinositol 3-kinase gamma/Janus kinase 2/MEK-1-dependent pathway. J Biol Chem 276:1211–1219

    PubMed  CAS  Google Scholar 

  • Cleeter MW, Cooper JM, Darley-Usmar VM, et al. (1994) Reversible inhibition of cytochrome c oxidase, the terminal enzyme of the mitochondrial respiratory chain, by nitric oxide. Implications for neurodegenerative diseases. FEBS Lett 345:50–54

    PubMed  CAS  Google Scholar 

  • Clementi E, Brown GC, Feelisch M, et al. (1998) Persistent inhibition of cell respiration by nitric oxide: crucial role of S-nitrosylation of mitochondrial complex I and protective action of glutathione. Proc Natl Acad Sci USA 95:7631–7636

    PubMed  CAS  Google Scholar 

  • Clementi E, Brown GC, Foxwell N, et al. (1999) On the mechanism by which vascular endothelial cells regulate their oxygen consumption. Proc Natl Acad Sci USA 96:1559–1562

    PubMed  CAS  Google Scholar 

  • Cohen RA (2005) The endothelium-derived hyperpolarizing factor puzzle. A mechanism without a mediator? Circulation 111:724–727

    PubMed  Google Scholar 

  • Cooke JP (2003) NO and angiogenesis. Atheroscler Suppl 4:53–60

    PubMed  CAS  Google Scholar 

  • Cornwell TL, Pryzwansky KB, Wyatt TA, et al. (1991) Regulation of sarcoplasmic reticulum protein phosphorylation by localized cyclic GMP-dependent protein kinase in vascular smooth muscle cells. Mol Pharmacol 40:923–931

    PubMed  CAS  Google Scholar 

  • Crane BR, Arvai AS, Gachhui R, et al. (1997) The structure of nitric oxide synthase oxygenase domain and inhibitor complexes. Science 278:425–431

    PubMed  CAS  Google Scholar 

  • Cromheeke KM, Kockx MM, De Meyer GR, et al. (1999) Inducible nitric oxide synthase colocalizes with signs of lipid oxidation/peroxidation in human atherosclerotic plaques. Cardiovasc Res 43:744–754

    PubMed  CAS  Google Scholar 

  • Cubberley RR, Alderton WK, Boyhan A, et al. (1997) Cysteine-200 of human inducible nitric oxide synthase is essential for dimerization of haem domains and for binding of haem, nitroarginine and tetrahydrobiopterin. Biochem J 323:131–146

    Google Scholar 

  • D’Uscio LV, Milstien S, Richardson D, et al. (2003) Long-termvitamin C treatment increases vascular tetrahydrobiopterin levels and nitric oxide synthase activity. Circ Res 92:88–95

    PubMed  CAS  Google Scholar 

  • Daff S, Sagami I, Shimizu T (1999) The 42-amino acid insert in the FMN domain of neuronal nitric-oxide synthase exerts control over Ca(2+)/calmodulin-dependent electron transfer. J Biol Chem 274:30589–30595

    PubMed  CAS  Google Scholar 

  • Davis ME, Grumbach IM, Fukai T, et al. (2004) Shear stress regulates endothelial nitricoxide synthase promoter activity through nuclear factor kappaB binding. J Biol Chem 279:163–168

    PubMed  CAS  Google Scholar 

  • De Caterina R, Libby P, Peng HB, et al. (1995) Nitric oxide decreases cytokine-induced endothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines. J Clin Invest 96:60–68

    PubMed  Google Scholar 

  • Dedio J, Konig P, Wohlfart P, et al. (2001) NOSIP, a novel modulator of endothelial nitric oxide synthase activity. FASEB J 15:79–89

    PubMed  CAS  Google Scholar 

  • De Meyer GR, Kockx MM, Cromheeke KM, et al. (2000) Periadventitial inducible nitric oxide synthase expression and intimal thickening. Arterioscler Thromb Vasc Biol 20:1896–1902

    PubMed  Google Scholar 

  • De Meyer GR, De Cleen DM, Cooper S, et al. (2002) Platelet phagocytosis and processing of beta-amyloid precursor protein as a mechanism of macrophage activation in atherosclerosis. Circ Res 90:1197–1204

    PubMed  Google Scholar 

  • Denninger JW, Marletta MA (1999) Guanylate cyclase and the NO/cGMP signaling pathway. Biochim Biophys Acta 1411:334–350

    PubMed  CAS  Google Scholar 

  • Dimmeler S, Fleming I, Fisslthaler B, et al. (1999) Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature 399:601–605

    PubMed  CAS  Google Scholar 

  • Ding H, Kubes P, Triggle C (2000) Potassium-and acetylcholine-induced vasorelaxation in mice lacking endothelial nitric oxide synthase. Br J Pharmacol 129:1194–1200

    PubMed  CAS  Google Scholar 

  • Djordjevic S, Roberts DL, Wang M (1995) Crystallization and preliminary X-ray studies of NADPH-cytochrome P450 reductase. Proc Natl Acad Sci USA 92:3214–3218

    PubMed  CAS  Google Scholar 

  • Dobrucki LW, Kalinowski L, Dobrucki IT, et al. (2001) Statin-stimulated nitric oxide release from endothelium. Med Sci Monit 7:622–627

    PubMed  CAS  Google Scholar 

  • Dunphy JT, Linder ME (1998) Signalling functions of protein palmitoylation. Biochem Biophys Acta 1436:245–261

    PubMed  CAS  Google Scholar 

  • Durante W, Schini VB, Scott-Burden T, et al. (1991) Platelet inhibition by an L-argininederived substance released by IL-1 beta-treated vascular smooth muscle cells. Am J Physiol 261:H2024–H2030

    PubMed  CAS  Google Scholar 

  • Endres M, Laufs U, Huang Z, et al. (1998) Stroke protection by 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors mediated by endothelial nitric oxide synthase. Proc Natl Acad Sci USA 95:8880–8885

    PubMed  CAS  Google Scholar 

  • Esaki T, Hayashi T, Muto E, et al. (1997) Expression of inducible nitric oxide synthase in T lymphocytes and macrophages of cholesterol-fed rabbits. Atherosclerosis 128:39–46

    PubMed  CAS  Google Scholar 

  • Fard A, Tuck CH, Donis JA, et al. (2000) Acute elevations of plasma asymmetric dimethylarginine and impaired endothelial function in response to a high-fat meal in patients with type 2 diabetes. Arterioscler Thromb Vasc Biol 20:2039–2044

    PubMed  CAS  Google Scholar 

  • Feng Y, Venema VJ, Venema RC, et al. (1999) VEGF-induced permeability increase is mediated by caveolae. Invest Ophthalmol Vis Sci 40:157–167

    PubMed  CAS  Google Scholar 

  • Feron O, Saldana F, Michel JB, et al. (1998) The endothelial nitric oxide synthase-caveolin regulatory cycle. J Biol Chem 273:3125–3128

    PubMed  CAS  Google Scholar 

  • Feron O, Dessy C, Moniotte S, et al. (1999) Hypercholesterolemia decreases nitric oxide production by promoting the interaction of caveolin and endothelial nitric oxide synthase. J Clin Invest 103:897–905

    PubMed  CAS  Google Scholar 

  • Fichtlscherer S, Dimmeler S, Breuer S, et al. (2004) Inhibition of cytochrome P450 2C9 improves endothelium-dependent, nitric oxide-mediated vasodilatation in patients with coronary artery disease. Circulation 109:178–183

    PubMed  CAS  Google Scholar 

  • Fischmann TO, Hruza A, Niu XD, et al. (1999) Structural characterization of nitric oxide synthase isoforms reveals striking active-site conservation. Nat Struct Biol 6:233–242

    PubMed  CAS  Google Scholar 

  • Fisslthaler B, Dimmeler S, Hermann C, et al. (2000) Phosphorylation and activation of the endothelial nitric oxide synthase by fluid shear stress. Acta Physiol Scand 168:81–88

    PubMed  CAS  Google Scholar 

  • Fisslthaler B, Benzing T, Busse R, et al. (2003) Insulin enhances the expression of the endothelial nitric oxide synthase in native endothelial cells: a dual role for Akt and AP-1. Nitric Oxide 8:253–261

    PubMed  CAS  Google Scholar 

  • Fleming I (2001) Cytochrome p450 and vascular homeostasis. Circ Res 89:753–762

    PubMed  CAS  Google Scholar 

  • Fleming I, Busse R (2003) Molecular mechanisms involved in the regulation of the endothelial nitric oxide synthase. Am J Physiol 284:R1–R12

    CAS  Google Scholar 

  • Fleming I, Fisslthaler B, Dimmeler S, et al. (2001) Phosphorylation of Thr495 regulates Ca2+/calmodulin-dependent endothelial nitric oxide synthase activity. Circ Res 88:e68–e75

    PubMed  CAS  Google Scholar 

  • Fleming I, Schulz C, Fichtlscherer B, et al. (2003) AMP-activated protein kinase (AMPK) regulates the insulin-induced activation of the nitric oxide synthase in human platelets. Thromb Haemost 90:863–871

    PubMed  CAS  Google Scholar 

  • Fliser D (2005) Asymmetric dimethylarginine (ADMA): the silent transition from an ‘uraemic toxin’ to a global cardiovascular risk molecule. Eur J Clin Invest 35:71–79

    PubMed  CAS  Google Scholar 

  • Förstermann U, Pollock JS, Schmidt HH, et al. (1991) Calmodulin-dependent endotheliumderived relaxing factor/nitric oxide synthase activity is present in the particulate and cytosolic fractions of bovine aortic endothelial cells. Proc Natl Acad Sci USA 88:1788–1792

    PubMed  Google Scholar 

  • Förstermann U, Closs EI, Pollock JS, et al. (1994) Nitric oxide synthase isozymes. Characterization, purification, molecular cloning and functions. Hypertension 23:1121–1131

    PubMed  Google Scholar 

  • Freedman JE, Sauter R, Battinelli EM, et al. (1999) Deficient platelet-derived nitric oxide and enhanced hemostasis in mice lacking the NOSIII gene. Circ Res 84:1416–1421

    PubMed  CAS  Google Scholar 

  • Frost MT, Wang Q, Moncada S, et al. (2005) Hypoxia accelerates nitric oxide-dependent inhibition of mitochondrial complex I in activated macrophages. Am J Physiol 288:R394–R400

    CAS  Google Scholar 

  • Fukuchi M, Giaid A (1999) Endothelial expression of endothelial nitric oxide synthase and endothelin-1 in human coronary artery disease. Specific reference to underlying lesion. Lab Invest 79:659–670

    PubMed  CAS  Google Scholar 

  • Fulton D, Gratton JP, McCabe TJ, et al. (1999) Regulation of endothelium-derived nitric oxide production by the protein kinase Akt. Nature 399:597–601

    PubMed  CAS  Google Scholar 

  • Fulton D, Babbitt R, Zoellner S, et al. (2004) Targeting of endothelial nitric oxide synthase to the cytoplasmic face of the golgi complex or plasma membrane regulates Akt-versus calcium-dependent mechanisms for nitric oxide release. J Biol Chem 279:30349–30357

    PubMed  CAS  Google Scholar 

  • Fung HL (2004) Biochemical mechanism of nitroglycerin action and tolerance: is this old mystery solved? Annu Rev Pharmacol Toxicol 44:67–85

    PubMed  CAS  Google Scholar 

  • Furchgott RF, Zawadzki JV (1980) The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288:373–376

    PubMed  CAS  Google Scholar 

  • Gaboury J, Woodman RC, Granger DN, et al. (1993) Nitric oxide prevents leukocyte adherence: role of superoxide. Am J Physiol 265:H862–H867

    PubMed  CAS  Google Scholar 

  • Gao S, Chen J, Brodsky SV, et al. (2004) Docking of endothelial nitric oxide synthase (eNOS) to the mitochondrial outer membrane: a pentabasic amino acid sequence in the autoinhibitory domain of eNOS targets a proteinase K-cleavable peptide on the cytoplasmic face of mitochondria. J Biol Chem 279:15968–15974

    PubMed  CAS  Google Scholar 

  • Garcia-Cardena G, Oh P, Liu J, et al. (1996) Targeting of nitric oxide synthase to endothelial cell caveolae via palmitoylation: implications for nitric oxide signaling. Proc Natl Acad Sci USA 93:6448–6453

    PubMed  CAS  Google Scholar 

  • Garcia-Cardena G, Fan R, Shah V, et al. (1998) Dynamic activation of endothelial nitric oxide synthase by Hsp90. Nature 392:821–824

    PubMed  CAS  Google Scholar 

  • Garg UC, Hassid A (1989) Nitric oxide-generating vasodilators and 8-bromo-cyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells. J Clin Invest 83:1774–1777

    PubMed  CAS  Google Scholar 

  • Gauthier TW, Davenpeck KL, Lefer AM (1994) Nitric oxide attenuates leukocyte-endothelial interaction via P-selectin in splanchnic ischemia-reperfusion. Am J Physiol 267:G562–G568

    PubMed  CAS  Google Scholar 

  • Geiger J, Nolte C, Walter U (1994) Regulation of calcium mobilization and entry in human platelets by endothelium-derived factors. Am J Physiol 267:C236–C244

    PubMed  CAS  Google Scholar 

  • Geller DA, Lowenstein CJ, Shapiro RA, et al. (1993) Molecular cloning and expression of inducible nitric oxide synthase from human hepatocytes. Proc Natl Acad Sci USA 90:3491–3495

    PubMed  CAS  Google Scholar 

  • Gewaltig MT, Kojda G (2002) Vasoprotection by nitric oxide: mechanisms and therapeutic potential. Cardiovasc Res 55:250–260

    PubMed  CAS  Google Scholar 

  • Ghafourifar P, Richter C (1997) Nitric oxide synthase activity in mitochondria. FEBS Lett 418:291–296

    PubMed  CAS  Google Scholar 

  • Giulivi C, Poderoso JJ, Boveris A (1998) Production of nitric oxide by mitochondria. J Biol Chem 273:11038–11043

    PubMed  CAS  Google Scholar 

  • Go YM, Park H, Maland MC, et al. (1998) Phosphatidylinositol 3-kinase β mediates shear stress-dependent activation of JNK in endothelial cells. Am J Physiol 275:H1898–H1904

    PubMed  CAS  Google Scholar 

  • Go YM, Gipp JJ, Mulcahy RT, et al. (2004) H2O2-dependent activation of GCLC-ARE4 reporter occurs by mitogen-activated protein kinase pathways without oxidation of cellular glutathione or thioredoxin-1. J Biol Chem 279:5837–5845

    PubMed  CAS  Google Scholar 

  • Govers R, Rabelink TJ (2001) Cellular regulation of endothelial nitric oxide synthase. Am J Physiol Renal Physiol 280:F193–F206

    PubMed  CAS  Google Scholar 

  • Govers R, van der Sluijs P, van Donselaar E, et al. (2002) Endothelial nitric oxide synthase and its negative regulator caveolin-1 localize to distinct perinuclear organelles. J Histochem Cytochem 50:779–788

    PubMed  CAS  Google Scholar 

  • Gow AJ, Stamler JS (1998) Reactions between nitric oxide and haemoglobin under physiological conditions. Nature 391:169–173

    PubMed  CAS  Google Scholar 

  • Gratton JP, Fontana J, O’Connor DS, et al. (2000) Reconstitution of an endothelial nitric oxide synthase (eNOS), hsp90, and caveolin-1 complex in vivo. J Biol Chem 275:22268–22272

    PubMed  CAS  Google Scholar 

  • Greenacre SA, Ischiropoulos H (2001) Tyrosine nitration: localization, quantification, consequences for protein function and signal transduction. Free Radic Res 34:541–581

    PubMed  CAS  Google Scholar 

  • Grisham MB, Jourd’Heuil D, Wink DA (1999) Nitric oxide. I. Physiological chemistry ofnitric oxide and its metabolites: implications in inflammation. Am J Physiol 276:G315–G321

    PubMed  CAS  Google Scholar 

  • Hagen T, Taylor CT, Lam F, et al. (2003) Redistribution of intracellular oxygen in hypoxia by nitric oxide: effect on HIF1α. Science 302:1975–1978

    PubMed  CAS  Google Scholar 

  • Harris MB, Ju H, Venema VJ, et al. (2001) Reciprocal phosphorylation and regulation of endothelial nitric oxide synthase in response to bradykinin stimulation. J Biol Chem 276:16587–16591

    PubMed  CAS  Google Scholar 

  • Hattori Y, Nakanishi N, Kasai K (2002) Statin enhances cytokine-mediated induction of nitric oxide synthesis in vascular smooth muscle cells. Cardiovasc Res 54:649–658

    PubMed  CAS  Google Scholar 

  • Heitzer T, Yla-Herttuala S, Luoma J, et al. (1996) Cigarette smoking potentiates endothelial dysfunction of forearm resistance vessels in patients with hypercholesterolemia. Role of oxidized LDL. Circulation 93:1346–1353

    PubMed  CAS  Google Scholar 

  • Hernandez-Perera O, Perez-Sala D, Navarro-Antolin J, et al. (1998) Effects of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, atorvastatin and simvastatin, on the expression of endothelin-1 and endothelial nitric oxide synthase in vascular endothelial cells. J Clin Invest 101:2711–2719

    PubMed  CAS  Google Scholar 

  • Hess DT, Matsumoto A, Kim SO, et al. (2005) Protein S-nitrosylation: purview and parameters. Nat Rev Mol Cell Biol 6:150–166

    PubMed  CAS  Google Scholar 

  • Hibbs JB, Taintor RR, Vavrin Z, et al. (1990) Synthesis of nitric oxide from a terminal guanidine nitrogen atom of L-arginine: a molecular mechanism regulating cellular proliferation that targets intracellular iron. In: Moncada S, Higgs EA (eds) Nitric oxide from L-arginine: a bioregulatory system. Elsevier, Amsterdam, pp 189–223

    Google Scholar 

  • Hingorani AD, Liang CF, Fatibene J, et al. (1999) A common variant of the endothelial nitric oxide synthase (Glu298Asp) is a major risk factor for coronary artery disease in the UK. Circulation 100:1515–1520

    PubMed  CAS  Google Scholar 

  • Hink U, Li H, Mollnau H, et al. (2001) Mechanisms underlying endothelial dysfunction in diabetes mellitus. Circ Res 88:E14–E22

    PubMed  CAS  Google Scholar 

  • Hobbs AJ, Higgs A, Moncada S (1999) Inhibition of nitric oxide synthase as a potential therapeutic target. Annu Rev Pharmacol Toxicol 39:191–220

    PubMed  CAS  Google Scholar 

  • Hood JD, Meininger CJ, Ziche M, et al. (1998) VEGF upregulates ecNOS message, protein, and NO production in human endothelial cells. Am J Physiol 274:H1054–H1058

    PubMed  CAS  Google Scholar 

  • Hoyer J, Köhler R, Distler A (1998) Mechanosensitive Ca2+ oscillations and STOC activation in endothelial cells. FASEB J 12:359–366

    PubMed  CAS  Google Scholar 

  • Huang A, Sun D, Koller A, et al. (1998) Gender difference in flow-induced dilation and regulation of shear stress: role of estrogen and nitric oxide. Am J Physiol 275:R1571–R1577

    PubMed  CAS  Google Scholar 

  • Huang A, Sun D, Carroll MA, et al. (2001) EDHF mediates flow-induced dilation in skeletal muscle arterioles of female eNOS-KO mice. Am J Physiol 280:H2462–H2469

    CAS  Google Scholar 

  • Huang PL, Huang Z, Mashimo H, et al. (1995) Hypertension in mice lacking the gene for endothelial nitric oxide synthase. Nature 377:239–242

    PubMed  CAS  Google Scholar 

  • Inoue N, Venema RC, Sayegh HS, et al. (1995) Molecular regulation of the bovine endothelial cell nitric oxide synthase by transforming growth factor-beta 1. Arterioscler Thromb Vasc Biol 15:1255–1261

    PubMed  CAS  Google Scholar 

  • Ito A, Tsao PS, Adimoolam S, et al. (1999) Novel mechanism for endothelial dysfunction: dysregulation of dimethylarginine dimethylaminohydrolase. Circulation 99:3092–3095

    PubMed  CAS  Google Scholar 

  • Jaffrey SR, Erdjument-Bromage H, Ferris CD, et al. (2001) Protein S-nitrosylation: a physiological signal for neuronal nitric oxide. Nat Cell Biol 3:193–197

    PubMed  CAS  Google Scholar 

  • Janssens S, Flaherty D, Nong Z, et al. (1998) Human endothelial nitric oxide synthase gene transfer inhibits vascular smooth muscle cell proliferation and neointima formation after balloon injury in rats. Circulation 97:1274–1281

    PubMed  CAS  Google Scholar 

  • Janssens SP, Shimouchi A, Quertermous T, et al. (1992) Cloning and expression of a cDNA encoding human endothelium-derived relaxing factor/nitric oxide synthase. J Biol Chem 267:14519–14522

    PubMed  CAS  Google Scholar 

  • Jenkins DC, Charles IG, Thomsen LL, et al. (1995) Roles of nitric oxide in tumor growth. Proc Natl Acad Sci USA 92:4392–4396

    PubMed  CAS  Google Scholar 

  • Jiang J, Cyr D, Babbitt RW, et al. (2003) Chaperone-dependent regulation of endothelial nitric oxide synthase intracellular trafficking by the co-chaperone/ubiquitin ligase CHIP. J Biol Chem 278:49332–49341

    PubMed  CAS  Google Scholar 

  • Jobin CM, Chen H, Lin AJ, et al. (2003) Receptor-regulated dynamic interaction between endothelial nitric oxide synthase and calmodulin revealed by fluorescence resonance energy transfer in living cells. Biochemistry 42:11716–11725

    PubMed  CAS  Google Scholar 

  • Kanai AJ, Pearce LL, Clemens PR, et al. (2001) Identification of a neuronal nitric oxide synthase in isolated cardiac mitochondria using electrochemical detection. Proc Natl Acad Sci USA 98:14126–14131

    PubMed  CAS  Google Scholar 

  • Kanwar S, Kubes P (1995) Nitric oxide is an antiadhesive molecule for leukocytes. New Horiz 3:93–104

    PubMed  CAS  Google Scholar 

  • Karantzoulis-Fegaras F, Antoniou H, Lai SL, et al. (1999) Characterization of the human endothelial nitric-oxide synthase promoter. J Biol Chem 274:3076–3093

    PubMed  CAS  Google Scholar 

  • Khan BV, Harrison DG, Olbrych MT, et al. (1996) Nitric oxide regulates vascular cell adhesion molecule 1 gene expression and redox-sensitive transcriptional events in human vascular endothelial cells. Proc Natl Acad Sci USA 93:9114–9119

    PubMed  CAS  Google Scholar 

  • Kilbourn RG, Jubran A, Gross SS, et al. (1990) Reversal of endotoxin-mediated shock by NG-methyl-L-arginine, an inhibitor of nitric oxide synthesis. Biochem Biophys Res Commun 172:1132–1138

    PubMed  CAS  Google Scholar 

  • Kim JW, Kang KW, Oh GT, et al. (2002) Induction of hepatic inducible nitric oxide synthase by cholesterol in vivo and in vitro. Exp Mol Med 34:137–144

    PubMed  CAS  Google Scholar 

  • Kimura S, Zhang GX, Nishiyama A (2005) Mitochondria-derived reactive oxygen species and vascular MAP kinases: comparison of angiotensin II and diazoxide. Hypertension 45:438–444

    PubMed  CAS  Google Scholar 

  • Knowles RG, Palacios M, Palmer RMJ, et al. (1989) Formation of nitric oxide from L-arginine in the central nervous system: a transduction mechanism for stimulation of the soluble guanylate cyclase. Proc Natl Acad Sci USA 86:5159–5162

    PubMed  CAS  Google Scholar 

  • Knowles RG, Salter M, Brooks SL, et al. (1990) Anti-inflammatory glucocorticoids inhibit the induction by endotoxin of nitric oxide synthase in the lung, liver and aorta of the rat. Biochem Biophys Res Commun 172:1042–1048

    PubMed  CAS  Google Scholar 

  • Kobzik L, Stringer B, Balligand JL, et al. (1995) Endothelial type nitric oxide synthase in skeletal muscle fibers: mitochondrial relationships. Biochem Biophys Res Commun 211:375–381

    PubMed  CAS  Google Scholar 

  • Kojda G, Cheng YC, Burchfield J, et al. (2001) Dysfunctional regulation of endothelial nitric oxide synthase (eNOS) expression in response to exercise in mice lacking one eNOS gene. Circulation 103:2839–2844

    PubMed  CAS  Google Scholar 

  • Korhonen R, Lahti A, Hamalainen M, et al. (2002) Dexamethasone inhibits inducible nitric oxide synthase expression and nitric oxide production by destabilizing mRNA in lipopolysaccharide-treated macrophages. Mol Pharmacol 62:698–704

    PubMed  CAS  Google Scholar 

  • Kroll J, Waltenberger J (1998) VEGF-A induces expression of eNOS and iNOS in endothelial cells via VEGF receptor-2 (KDR). Biochem Biophys Res Commun 252:743–746

    PubMed  CAS  Google Scholar 

  • Kubes P (1995) Nitric oxide affects microvascular permeability in the intact and inflamed vasculature. Microcirculation 2:235–244

    PubMed  CAS  Google Scholar 

  • Kubes P, Suzuki M, Granger DN (1991) Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci USA 88:4651–4655

    PubMed  CAS  Google Scholar 

  • Kuhlencordt PJ, Gyurko R, Han F, et al. (2001a) Accelerated atherosclerosis, aortic aneurysm formation, and ischemic heart disease in apolipoprotein E/endothelial nitric oxide synthase double-knockout mice. Circulation 104:448–454

    PubMed  CAS  Google Scholar 

  • Kuhlencordt PJ, Chen J, Han F, et al. (2001b) Genetic deficiency of inducible nitric oxide synthase reduces atherosclerosis and lowers plasma lipid peroxides in apolipoprotein E-knockout mice. Circulation 103:3099–3104

    PubMed  CAS  Google Scholar 

  • Kuhlencordt PJ, Rosel E, Gerszten RE, et al. (2004) Role of endothelial nitric oxide synthase in endothelial activation: insights from eNOS knockout endothelial cells. Am J Physiol 286:C1195–C1202

    CAS  Google Scholar 

  • Kureishi Y, Luo Z, Shiojima I, et al. (2000) The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals. Nat Med 6:1004–1010

    PubMed  CAS  Google Scholar 

  • Kurihara N, Alfie ME, Sigmon DH, et al. (1998) Role of nNOS in blood pressure regulation in eNOS null mutant mice. Hypertension 32:856–861

    PubMed  CAS  Google Scholar 

  • Kurtz A, Wagner C (1998) Role of nitric oxide in the control of renin secretion. Am J Physiol 275:F849–F862

    PubMed  CAS  Google Scholar 

  • Lablanche JM, Grollier G, Lusson JR, et al. (1997) Effect of the direct nitric oxide donors linsidomine and molsidomine on angiographic restenosis after coronary balloon angioplasty. The ACCORD Study. Angioplastic Coronaire Corvasal Diltiazem. Circulation 95:83–89

    PubMed  Google Scholar 

  • Lamas S, Marsden PA, Li GK, et al. (1992) Endothelial nitric oxide synthase: molecular cloning and characterization of a distinct constitutive enzyme isoform. Proc Natl Acad Sci USA 89:6348–6352

    PubMed  CAS  Google Scholar 

  • Landmesser U, Dikalov S, Price SR, et al. (2003) Oxidation of tetrahydrobiopterin leads to uncoupling of endothelial cell nitric oxide synthase in hypertension. J Clin Invest 111:1201–1209

    PubMed  CAS  Google Scholar 

  • Lane P, Gross SS (2002) Disabling a C-terminal autoinhibitory control element in endothelial nitric-oxide synthase by phosphorylation provides a molecular explanation for activation of vascular NO synthesis by diverse physiological stimuli. J Biol Chem 277:19087–19094

    PubMed  CAS  Google Scholar 

  • Lane P, Hao G, Gross SS (2001) S-nitrosylation is emerging as a specific and fundamental post-translational protein modification: head-to-head comparison with O-phosphorylation. Sci STKE 86:RE1

    Google Scholar 

  • Lantoine F, Brunet A, Bedioui F, et al. (1995) Direct measurement of nitric oxide production in platelets: relationship with cytosolic Ca2+ concentration. Biochem Biophys Res Commun 215:842–848

    PubMed  CAS  Google Scholar 

  • Laszlo F, Whittle BJR, Moncada S (1994) Time-dependent enhancement or inhibition of endotoxin-induced vascular injury in rat intestine by nitric oxide synthase inhibitors. Br J Pharmacol 111:1309–1315

    PubMed  CAS  Google Scholar 

  • Laufs U, Fata VL, Liao JK (1997) Inhibition of 3-hydroxy-methylglutaryl (HMG)-CoA reductase blocks hypoxia-mediated down-regulation of endothelial nitric oxide synthase. J Biol Chem 272:31725–31729

    PubMed  CAS  Google Scholar 

  • Leibovich SJ, Polverini PJ, Fong TW, et al. (1994) Production of angiogenic activity by human monocytes requires an L-arginine/nitric oxide-synthase-dependent effector mechanism. Proc Natl Acad Sci USA 91:4190–4194

    PubMed  CAS  Google Scholar 

  • Leiper JM, Santa Maria J, Chubb A, et al. (1999) Identification of two human dimethylarginine dimethylaminohydrolases with distinct tissue distributions and homology with microbial arginine deiminases. Biochem J 343:209–214

    PubMed  CAS  Google Scholar 

  • Leopold JA, Loscalzo J (2005) Oxidative enzymopathies and vascular disease. Arterioscler Thromb Vasc Biol 25:1332–1340

    PubMed  CAS  Google Scholar 

  • Levine GN, Frei B, Koulouris SN, et al. (1996) Ascorbic acid reverses endothelial vasomotor dysfunction in patients with coronary artery disease. Circulation 93:1107–1113

    PubMed  CAS  Google Scholar 

  • Lin MI, Fulton D, Babbitt R, et al. (2003) Phosphorylation of threonine 497 in endothelial nitric oxide synthase coordinates the coupling of L-arginine metabolism to efficient nitric oxide production. J Biol Chem 278:44719–44726

    PubMed  CAS  Google Scholar 

  • Liu J, Garcia Cardena G, Sessa WC (1995) Biosynthesis and palmitoylation of endothelial nitric oxide synthase: mutagenesis of palmitoylation sites, cysteines-15 and/or-26, argues against depalmitoylation-induced translocation of the enzyme. Biochemistry 34:12333–12340

    PubMed  CAS  Google Scholar 

  • Liu J, Hughes TE, Sessa WC (1997) The first 35 amino acids and fatty acylation sites determine the molecular targeting of endothelial nitric oxide synthase into the golgi region of cells: a green fluorescent protein study. J Cell Biol 137:1525–1535

    PubMed  CAS  Google Scholar 

  • Lopez-Ongil S, Hernandez-Perera O, Navarro-Antolin J, et al. (1998) Role of reactive oxygen species in the signalling cascade of cyclosporine A-mediated up-regulation of eNOS in vascular endothelial cells. Br J Pharmacol 124:447–454

    PubMed  CAS  Google Scholar 

  • Lu JL, Schmiege LM 3rd, Kuo L, et al. (1996) Downregulation of endothelial constitutive nitric oxide synthase expression by lipopolysaccharide. Biochem Biophys Res Commun 225:1–5

    PubMed  CAS  Google Scholar 

  • Lu TM, Ding YA, Charng MJ, et al. (2003) Asymmetrical dimethylarginine: a novel risk factor for coronary artery disease. Clin Cardiol 26:458–464

    PubMed  Google Scholar 

  • Luckhoff A, Pohl U, Mulsch A, et al. (1988) Differential role of extra-and intracellular calcium in the release of EDRF and prostacyclin from cultured endothelial cells. Br J Pharmacol 95:189–196

    PubMed  CAS  Google Scholar 

  • Luo Z, Fujio Y, Kureishi Y, et al. (2000) Acute modulation of endothelial Akt/PKB activity alters nitric oxide-dependent vasomotor activity in vivo. J Clin Invest 106:493–499

    PubMed  CAS  Google Scholar 

  • Luoma JS, Stralin P, Marklund SL, et al. (1998) Expression of extracellular SOD and iNOS in macrophages and smooth muscle cells in human and rabbit atherosclerotic lesions: colocalization with epitopes characteristic of oxidized LDL and peroxynitrite-modified proteins. Arterioscler Thromb Vasc Biol 18:157–167

    PubMed  CAS  Google Scholar 

  • Luscher TF, Tanner FC, Tschudi MR, et al. (1993) Endothelial dysfunction in coronary artery disease. Annu Rev Med 44:395–418

    PubMed  CAS  Google Scholar 

  • MacNaul KL, Hutchinson NI (1993) Differential expression of iNOS and cNOS mRNA in human vascular smooth muscle cells and endothelial cells under normal and inflammatory conditions. Biochem Biophys Res Commun 196:1330–1334

    PubMed  CAS  Google Scholar 

  • Malinski T, Radomski MW, Taha Z, et al. (1993) Direct electrochemical measurement of nitric oxide released from human platelets. Biochem Biophys Res Commun 194:960–965

    PubMed  CAS  Google Scholar 

  • Mann GE, Yudilevich DL, Sobrevia L (2003) Regulation of amino acid and glucose transporters in endothelial and smooth muscle cells. Physiol Rev 83:183–252

    PubMed  CAS  Google Scholar 

  • Mannick JB, Hausladen A, Liu L, et al. (1999) Fas-induced caspase denitrosylation. Science 284:651–654

    PubMed  CAS  Google Scholar 

  • Marrero MB, Venema VJ, Ju H, et al. (1999) Endothelial nitric oxide synthase interactions with G-protein-coupled receptors. Biochem J 343:335–340

    PubMed  CAS  Google Scholar 

  • Marsden PA, Shappert KT, Chen HS, et al. (1992) Molecular cloning and characterization of human endothelial nitric oxide synthase. FEBS Lett 307:287–293

    PubMed  CAS  Google Scholar 

  • Marsden PA, Heng HH, Scherer SW, et al. (1993) Structure and chromosomal localization of the human constitutive endothelial nitric oxide synthase gene. J Biol Chem 268:17478–17488

    PubMed  CAS  Google Scholar 

  • Massberg S, Sausbier M, Klatt P, et al. (1999) Increased adhesion and aggregation of platelets lacking cyclic guanosine 3′,5′-monophosphate kinase I. J Exp Med 189:1255–1264

    PubMed  CAS  Google Scholar 

  • Massion PB, Feron O, Dessy C, et al. (2003) Nitric oxide and cardiac function: ten years after, and continuing. Circ Res 93:388–398

    PubMed  CAS  Google Scholar 

  • Matsumura M, Kakishita H, Suzuki M, et al. (2001) Dexamethasone suppresses iNOS gene expression by inhibiting NF-κB in vascular smooth muscle cells. Life Sci 69:1067–1077

    PubMed  CAS  Google Scholar 

  • Mattson DL, Bellehumeur TG (1996) Neural nitric oxide synthase in the renal medulla and blood pressure regulation. Hypertension 28:297–303

    PubMed  CAS  Google Scholar 

  • Mattson DL, Lu S, Cowley AW Jr (1997) Role of nitric oxide in the control of the renal medullary circulation. Clin Exp Pharmacol Physiol 24:587–590

    PubMed  CAS  Google Scholar 

  • Maxwell AJ (2002) Mechanisms of dysfunction of the nitric oxide pathway in vascular diseases. Nitric Oxide 6:101–124

    PubMed  CAS  Google Scholar 

  • McCabe TJ, Fulton D, Roman LJ, et al. (2000) Enhanced electron flux and reduced calmodulin dissociation may explain “calcium-independent” eNOS activation by phosphorylation. J Biol Chem 275:6123–6128

    PubMed  CAS  Google Scholar 

  • Mete A, Connolly S (2003) Inhibitors of the NOS enzymes: a patent review. I Drugs 6:57–65

    PubMed  CAS  Google Scholar 

  • Michel T, Gordon K, Busconi L (1993) Phosphorylation and subcellular translocation of endothelial nitric oxide synthase. Proc Natl Acad Sci USA 90:6252–6256

    PubMed  CAS  Google Scholar 

  • Michell BJ, Chen Z, Tiganis T, et al. (2001) Coordinated control of endothelial NO synthase phosphorylation by protein kinase C and the cAMP-dependent protein kinase. J Biol Chem 276:17625–17628

    PubMed  CAS  Google Scholar 

  • Mitchell JA, Förstermann U, Warner TD, et al. (1991) Endothelial cells have a particulate enzyme system responsible for EDRF formation: measurement by vascular relaxation. Biochem Biophys Res Commun 176:1417–1423

    PubMed  CAS  Google Scholar 

  • Miyamoto Y, Saito Y, Kajiyama N, et al. (1998) Endothelial nitric oxide synthase gene is positively associated with essential hypertension. Hypertension 32:3–8

    PubMed  CAS  Google Scholar 

  • Moncada S (1989) Introduction. In: Moncada S, Higgs EA (eds) Nitric oxide from L-arginine: a bioregulatory system. Elsevier, Amsterdam, pp 1–4

    Google Scholar 

  • Moncada S (2006) Adventures in vascular biology: a tale of two mediators. Phil Trans Roy Soc B 361:735–759

    CAS  Google Scholar 

  • Moncada S, Erusalimsky JD (2002) Does nitric oxide modulate mitochondrial energy generation and apoptosis? Nat Rev Mol Cell Biol 3:214–220

    PubMed  CAS  Google Scholar 

  • Moncada S, Higgs EA (2006) The discovery of nitric oxide and its role in vascular biology. Br J Pharmacol 147:S193–S201

    PubMed  CAS  Google Scholar 

  • Moncada S, Palmer RM, Higgs EA (1989) Biosynthesis of nitric oxide from L-arginine. A pathway for the regulation of cell function and communication. Biochem Pharmacol 38:1709–1715

    PubMed  CAS  Google Scholar 

  • Moncada S, Palmer RMJ, Higgs EA (1991) Nitric oxide: physiology, pathophysiology and pharmacology. Pharmacol Rev 43:109–142

    PubMed  CAS  Google Scholar 

  • Moroi M, Zhang L, Yasuda T, et al. (1998) Interaction of genetic deficiency of endothelial nitric oxide, gender, and pregnancy in vascular response to injury in mice. J Clin Invest 101:1225–1232

    PubMed  CAS  Google Scholar 

  • Morris SM Jr, Billiar TR (1994) New insights into the regulation of inducible nitric oxide synthesis. Am J Physiol 266:E829–E839

    PubMed  CAS  Google Scholar 

  • Mueller CF, Laude K, McNally JS, et al. (2005) Redox mechanisms in blood vessels. Arterioscler Thromb Vasc Biol 25:274–278

    PubMed  CAS  Google Scholar 

  • Munzel T, Kurz S, Heitzer T, et al. (1996) New insights into mechanisms underlying nitrate tolerance. Am J Cardiol 77:24C–30C

    PubMed  CAS  Google Scholar 

  • Muruganandam A, Mutus B (1994) Isolation of nitric oxide synthase from human platelets. Biochim Biophys Acta 1200:1–6

    PubMed  CAS  Google Scholar 

  • Nagareddy PR, Xia Z, McNeill JH, et al. (2005) Increased expression of iNOS is associated with endothelial dysfunction and impaired pressor responsiveness in streptozotocin-induced diabetes. Am J Physiol Heart Circ Physiol 289:H2144–H2152

    PubMed  CAS  Google Scholar 

  • Nakane M, Schmidt HH, Pollock JS, et al. (1993) Cloned human brain nitric oxide synthase is highly expressed in skeletal muscle. FEBS Lett 316:175–180

    PubMed  CAS  Google Scholar 

  • Nakayama T, Soma M, Takahashi Y, et al. (1997) Association analysis of CA repeat polymorphism of the endothelial nitric oxide synthase gene with essential hypertension in Japanese. Clin Genet 51:26–30

    PubMed  CAS  Google Scholar 

  • Nathan C, Xie QW (1994) Nitric oxide synthases: roles, tolls and controls. Cell 78:915–918

    PubMed  CAS  Google Scholar 

  • Navarro J, Sanchez A, Saiz J, et al. (1994) Hormonal, renal and metabolic alterations during hypertension induced by chronic inhibition of NO in rats. Am J Physiol 267:R1516–R1521

    PubMed  CAS  Google Scholar 

  • Navarro-Antolin J, Rey-Campos J, Lamas S (2000) Transcriptional induction of endothelial nitric oxide gene by cyclosporine A. A role for activator protein-1. J Biol Chem 275:3075–3080

    PubMed  CAS  Google Scholar 

  • Nedvetsky PI, Sessa WC, Schmidt HH (2002) There’s NO binding like NOS binding: protein-protein interactions in NO/cGMP signaling. Proc Natl Acad Sci USA 99:16510–16512

    PubMed  CAS  Google Scholar 

  • Neunteufl T, Heher S, Katzenschlager R, et al. (2000) Late prognostic value of flow-mediated dilation in the brachial artery of patients with chest pain. Am J Cardiol 86:207–210

    PubMed  CAS  Google Scholar 

  • Nishida CR, Ortiz de Montellano PR (1999) Autoinhibition of endothelial nitric-oxide synthase. Identificationof an electrontransfer control element. J Biol Chem 274:14692–14698

    PubMed  CAS  Google Scholar 

  • Nishida K, Harrison DG, Navas JP, et al. (1992) Molecular cloning and characterization of the constitutive bovine aortic endothelial cell nitric oxide synthase. J Clin Invest 90:2092–2096

    PubMed  CAS  Google Scholar 

  • Nisoli E, Clementi E, Paolucci C, et al. (2003) Mitochondrial biogenesis in mammals: the role of endogenous nitric oxide. Science 299:896–899

    PubMed  CAS  Google Scholar 

  • Nisoli E, Tonello C, Cardile A, et al. (2005) Calorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS. Science 310:314–317

    PubMed  CAS  Google Scholar 

  • Ohashi Y, Kawashima S, Hirata K, et al. (1998) Hypotension and reduced nitric oxide-elicited vasorelaxation in transgenic mice overexpressing endothelial nitric oxide synthase. J Clin Invest 102:2061–2071

    PubMed  CAS  Google Scholar 

  • Ortiz PA, Garvin JL (2003) Cardiovascular and renal control in NOS-deficient mouse models. Am J Physiol 284:R628–R638

    CAS  Google Scholar 

  • Ortiz PA, Hong NJ, Garvin JL (2001) NO decreases thick ascending limb chloride absorption by reducing Na+-K+-2Cl-cotransporter activity. Am J Physiol 281:F819–F825

    CAS  Google Scholar 

  • Palacios-Callender M, Quintero M, Hollis VS, et al. (2004) Endogenous NO regulates superoxide production at low oxygen concentrations by modifying the redox state of cytochrome c oxidase. Proc Natl Acad Sci USA 101:7630–7635

    PubMed  CAS  Google Scholar 

  • Pallone TL, Mattson DL (2002) Role of nitric oxide in regulation of the renal medulla in normal and hypertensive kidneys. Curr Opin Nephrol Hypertens 11:93–98

    PubMed  Google Scholar 

  • Palmer RM, Ferrige AG, Moncada S (1987) Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327:524–526

    PubMed  CAS  Google Scholar 

  • Palmer RM, Ashton DS, Moncada S (1988) Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature 333:664–666

    PubMed  CAS  Google Scholar 

  • Palmer RMJ, Moncada S (1989) A novel citrulline-forming enzyme implicated in the formation of nitric oxide by vascular endothelial cells. Biochem Biophys Res Commun 158:348–352

    PubMed  CAS  Google Scholar 

  • Papapetropoulos A, Garcia-Cardena G, Madri JA, et al. (1997) Nitric oxide production contributes to the angiogenic properties of vascular endothelial growth factor in human endothelial cells. J Clin Invest 100:3131–3139

    PubMed  CAS  Google Scholar 

  • Paulus WJ, Shah AM (1999) NO and cardiac diastolic function. Cardiovasc Res 43:595–606

    PubMed  CAS  Google Scholar 

  • Pelligrino DA, Ye S, Tan F, et al. (2000) Nitric oxide-dependent pial arteriolar dilation in the female rat: effects of chronic estrogen depletion and repletion. Biochem Biophys Res Commun 269:165–171

    PubMed  CAS  Google Scholar 

  • Perez-Mato I, Castro C, Ruiz FA, et al. (1999) Methionine adenosyltransferase S-nitrosylation is regulated by the basic and acidic amino acids surrounding the target thiol. J Biol Chem 274:17075–17079

    PubMed  CAS  Google Scholar 

  • Persichini T, Mazzone V, Polticelli F, et al. (2005) Mitochondrial type I nitric oxide synthase physically interacts with cytochrome c oxidase. Neurosci Lett 384:254–259

    PubMed  CAS  Google Scholar 

  • Petroff MG, Kim SH, Pepe S, et al. (2001) Endogenous nitric oxide mechanisms mediate the stretch dependence of Ca2+ release in cardiomyocytes. Nat Cell Biol 3:867–873

    PubMed  CAS  Google Scholar 

  • Pfeifer A, Klatt P, Massberg S, et al. (1998) Defective smooth muscle regulation in cGMP kinase I-deficient mice. EMBO J 17:3045–3051

    PubMed  CAS  Google Scholar 

  • Poderoso JJ, Carreras MC, Lisdero C, et al. (1996) Nitric oxide inhibits electron transfer and increases superoxide radical production in rat heart mitochondria and submitochondrial particles. Arch Biochem Biophys 328:85–92

    PubMed  CAS  Google Scholar 

  • Pollock JS, Förstermann U, Mitchell JA, et al. (1991) Purification and characterization of particulate endothelium-derived relaxing factor synthase from cultured and native bovine aortic endothelial cells. Proc Natl Acad Sci USA 88:10480–10484

    PubMed  CAS  Google Scholar 

  • Pollock JS, Klinghofer V, Förstermann U, et al. (1992) Endothelial nitric oxide synthase is myristoylated. FEBS Lett 309:402–404

    PubMed  CAS  Google Scholar 

  • Prabhakar P, Cheng V, Michel T (2000) A chimeric transmembrane domain directs endothelial nitric oxide synthase palmitoylation and targeting to plasmalemmal caveolae. J Biol Chem 275:19416–19421

    PubMed  CAS  Google Scholar 

  • Pritchard KA Jr, Ackerman AW, Gross ER, et al. (2001) Heat shock protein 90 mediates the balance of nitric oxide and superoxide anion from endothelial nitric oxide synthase. J Biol Chem 276:17621–17624

    PubMed  CAS  Google Scholar 

  • Quintero M, Colombo S, Godfrey A, Moncada S (2006) Mitochondria as signaling organelles in the vascular endothelium. Proc Natl Acad Sci USA 103:5379–5384

    PubMed  CAS  Google Scholar 

  • Radomski MW, Palmer RMJ, Moncada S (1987a) Comparative pharmacology of endothelium-derived relaxing factor, nitric oxide and prostacyclin in platelets. Br J Pharmacol 92:181–187

    PubMed  CAS  Google Scholar 

  • Radomski MW, Palmer RMJ, Moncada S (1987b) The role of nitric oxide and cGMP in platelet adhesion to vascular endothelium. Biochem Biophys Res Commun 148:1482–1489

    PubMed  CAS  Google Scholar 

  • Radomski MW, Palmer RMJ, Moncada S (1987c) The anti-aggregating properties of vascular endothelium: interactions between prostacyclin and nitric oxide. Br J Pharmacol 92:639–646

    PubMed  CAS  Google Scholar 

  • Radomski MW, Palmer RMJ, Moncada S (1990a) Glucocorticoids inhibit the expression of an inducible, but not the constitutive, nitric oxide synthase in vascular endothelial cells. Proc Natl Acad Sci USA 87:10043–10047

    PubMed  CAS  Google Scholar 

  • Radomski MW, Palmer RMJ, Moncada S (1990b) An L-arginine/nitric oxide pathway present in human platelets regulates aggregation. Proc Natl Acad Sci USA 87:5193–5197

    PubMed  CAS  Google Scholar 

  • Radomski MW, Palmer RMJ, Moncada S (1990c) Characterization of the L-arginine:nitric oxide pathway in human platelets. Br J Pharmacol 101:325–328

    PubMed  CAS  Google Scholar 

  • Rajagopalan S, Kurz S, Munzel T, et al. (1996) Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. Contribution to alterations of vasomotor tone. J Clin Invest 97:1916–1923

    PubMed  CAS  Google Scholar 

  • Raman CS, Li H, Martasek P, Kral V, et al. (1998) Crystal structure of constitutive endothelial nitric oxide synthase: a paradigm for pterin function involving a novel metal center. Cell 95:939–950

    PubMed  CAS  Google Scholar 

  • Randiramboavonjy V, Schrader J, Busse R, et al. (2004) Insulin induces the release of vasodilator compounds from platelets by a nitric oxide-G-kinase-VAMP-3-dependent pathway. J Exp Med 199:347–356

    Google Scholar 

  • Rao GH, Krishnamurthi S, Raij L, et al. (1990) Influence of nitric oxide on agonist-mediated calcium mobilization in platelets. Biochem Med Metab Biol 43:271–275

    PubMed  CAS  Google Scholar 

  • Razani B, Engelman JA, Wang XB, et al. (2001) Caveolin-1 null mice are viable but show evidence of hyperproliferative and vascular abnormalities. J Biol Chem 276:38121–38138

    PubMed  CAS  Google Scholar 

  • Reddy KG, Nair RN, Sheehan HM, et al. (1994) Evidence that selective endothelial dysfunction may occur in the absence of angiographic or ultrasound atherosclerosis in patients with risk factors for atherosclerosis. J Am Coll Cardiol 23:833–843

    PubMed  CAS  Google Scholar 

  • Rees DD, Palmer RMJ, Moncada S (1989) Role of endothelium-derived nitric oxide in the regulation of blood pressure. Proc Natl Acad Sci USA 86:3375–3378

    PubMed  CAS  Google Scholar 

  • Rees DD, Higgs EA, Moncada S (2000) Nitric oxide and the vessel wall. In: Colman RW, Hirsch J, Marder VJ, Clowes AW, George NJ (eds) Hemostasis and thrombosis. Lippincott Williams and Wilkins, Philadelphia, pp 673–682

    Google Scholar 

  • Robinson LJ, Michel T (1995) Mutagenesis of palmitoylation sites in endothelial nitric oxide synthase identifies a novel motif for dual acylation and subcellular targeting. Proc Natl Acad Sci USA 92:11776–11780

    PubMed  CAS  Google Scholar 

  • Robinson LJ, Busconi L, Michel T (1995) Agonist-modulated palmitoylation of endothelial nitric oxide synthase. J Biol Chem 270:995–998

    PubMed  CAS  Google Scholar 

  • Rosenkranz-Weiss P, Sessa WC, Milstien S, et al. (1994) Regulation of nitric oxide synthesis by proinflammatory cytokines in human umbilical vein endothelial cells. Elevations in tetrahydrobiopterin levels enhance endothelial nitric oxide synthase specific activity. J Clin Invest 93:2236–2243

    PubMed  CAS  Google Scholar 

  • Russell KS, Haynes MP, Caulin-Glaser T, et al. (2000) Estrogen stimulates heat shock protein 90 binding to endothelial nitric oxide synthase in human vascular endothelial cells. Effects on calcium sensitivity and NO release. J Biol Chem 275:5026–5030

    PubMed  CAS  Google Scholar 

  • Salerno JC, Harris DE, Irizarry K, et al. (1997) An autoinhibitory control element defines calcium-regulated isoforms of nitric oxide synthase. J Biol Chem 272:29769–29777

    PubMed  CAS  Google Scholar 

  • Santolini J, Meade AL, Stuehr DJ (2001) Differences in three kinetic parameters underpin the unique catalytic profiles of nitric-oxide synthases I, II, and III. J Biol Chem 276:48887–48898

    PubMed  CAS  Google Scholar 

  • Saura M, Zaragoza C, Cao W, et al. (2002) Smad2 mediates transforming growth factor-beta induction of endothelial nitric oxide synthase expression. Circ Res 91:806–813

    PubMed  CAS  Google Scholar 

  • Sausbier M, Schubert R, Voigt V, et al. (2000) Mechanisms of NO/cGMP-dependent vasorelaxation. Circ Res 87:825–830

    PubMed  CAS  Google Scholar 

  • Schachinger V, Britten MB, Zeiher AM (2000) Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease. Circulation 101:1899–1906

    PubMed  CAS  Google Scholar 

  • Schlossmann J, Hofmann F (2005) cGMP-dependent protein kinases in drug discovery. Drug Discov Today 10:627–634

    PubMed  CAS  Google Scholar 

  • Schlossmann J, Ammendola A, Ashman K, et al. (2000) Regulation of intracellular calcium by a signalling complex of IRAG, IP3 receptor and cGMP kinase Iβ. Nature 404:197–201

    PubMed  CAS  Google Scholar 

  • Schmidt H, Hofmann H, Schindler U, et al. (1996) No NO from NO synthase. Proc Natl Acad Sci USA 93:14492–14497

    PubMed  CAS  Google Scholar 

  • Schneider MP, Erdmann J, Delles C, et al. (2000) Functional gene testing of the Glu298Asp polymorphism of the endothelial NO synthase. J Hypertens 18:1767–1773

    PubMed  CAS  Google Scholar 

  • Schwarz UR, Walter U, Eigenthaler M (2001) Taming platelets with cyclic nucleotides. Biochem Pharmacol 62:1153–1161

    PubMed  CAS  Google Scholar 

  • Schweizer M, Richter C (1994) Nitricoxide potently and reversibly deenergizes mitochondria at low oxygen tension. Biochem Biophys Res Commun 204:169–175

    PubMed  CAS  Google Scholar 

  • Scotland RS, Chauhan S, Vallance PJ, et al. (2001) An endothelium-derived hyperpolarizing factor-like factor moderates myogenic constriction of mesenteric resistance arteries in the absence of endothelial nitric oxide synthase-derived nitric oxide. Hypertension 38:833–839

    PubMed  CAS  Google Scholar 

  • Scotland RS, Morales-Ruiz M, Chen Y, et al. (2002) Functional reconstitution of endothelial nitric oxide synthase reveals the importance of serine 1179 in endothelium-dependent vasomotion. Circ Res 90:904–910

    PubMed  CAS  Google Scholar 

  • Scotland RS, Madhani M, Chauhan S, et al. (2005) Investigation of vascular responses in endothelial nitric oxide synthase/cyclooxygenase-1 double-knockout mice. Key role for endothelium-derived hyperpolarizing factor in the regulation of blood pressure in vivo. Circulation 111:796–803

    PubMed  CAS  Google Scholar 

  • Sessa WC (2004) eNOS at a glance. J Cell Sci 117:2427–2429

    PubMed  CAS  Google Scholar 

  • Sessa WC, Harrison JK, Barber CM, et al. (1992) Molecular cloning and expression of a cDNA encoding endothelial cell nitric oxide synthase. J Biol Chem 267:15274–15276

    PubMed  CAS  Google Scholar 

  • Shaul PA, Smart EJ, Robinson LJ, et al. (1996) Acylation targets endothelial nitric-oxide synthase to plasmalemmal caveolae. J Biol Chem 271:6518–6522

    PubMed  CAS  Google Scholar 

  • Sherman PA, Laubach VE, Reep BR, et al. (1993) Purification and cDNA sequence of an inducible nitric oxide synthase from a human tumor cell line. Biochemistry 32:11600–11605

    PubMed  CAS  Google Scholar 

  • Shesely EG, Maeda N, Kim HS, et al. (1996) Elevated blood pressures in mice lacking endothelial nitric oxide synthase. Proc Natl Acad Sci USA 93:13176–13181

    PubMed  CAS  Google Scholar 

  • Shimasaki Y, Yasue H, Yoshimura M, et al. (1998) Association of the missense Glu298Asp variant of the endothelial nitric oxide synthase gene with myocardial infarction. J Am Coll Cardiol 31:1506–1510

    PubMed  CAS  Google Scholar 

  • Siddhanta U, Wu C, Abu-Soud HM, et al. (1996) Hemeiron reduction and catalysis by a nitric oxide synthase heterodimer containing one reductase and two oxygenase domains. J Biol Chem 271:7309–7312

    PubMed  CAS  Google Scholar 

  • Silacci P, Formentin K, Bouzourene K, et al. (2000) Unidirectional and oscillatory shear stress differentially modulate NOS III gene expression. Nitric Oxide 4:47–56

    PubMed  CAS  Google Scholar 

  • Simon DI, Stamler JS, Loh E, et al. (1995) Effect of nitric oxide synthase inhibition on bleeding time in humans. J Cardiovasc Pharmacol 26:339–342

    PubMed  CAS  Google Scholar 

  • Simoncini T, Hafezi-Moghadam A, Brazil DP, et al. (2000) Interaction of oestrogen receptor with the regulatory subunit of phosphatidylinositol-3-OH kinase. Nature 407:538–541

    PubMed  CAS  Google Scholar 

  • Slater TF (1972) Free radical mechanisms in tissue injury. Pion, London

    Google Scholar 

  • Solzbach U, Hornig B, Jeserich M, et al. (1997) Vitamin C improves endothelial dysfunction of epicardial coronary arteries in hypertensive patients. Circulation 96:1513–1519

    PubMed  CAS  Google Scholar 

  • Sowa G, Liu J, Papapetropoulos A, et al. (1999) Trafficking of endothelial nitric oxide synthase in living cells. J Biol Chem 274:22524–22531

    PubMed  CAS  Google Scholar 

  • Stagliano NE, Zhao W, Prado R, et al. (1997) The effect of nitric oxide synthase inhibition on acute platelet accumulation and hemodynamic depression in a rat model of thromboembolic stroke. J Cereb Blood Flow Metab 17:1182–1190

    PubMed  CAS  Google Scholar 

  • Stamler JS, Hausladen A (1998) Oxidative modifications in nitrosative stress. Nat Struct Biol 5:247–249

    PubMed  CAS  Google Scholar 

  • Stamler JS, Simon DI, Osborne JA, et al. (1992) S-nitrosylation of proteins with nitric oxide: synthesis and characterization of biologically active compounds. Proc Natl Acad Sci USA 89:444–448

    PubMed  CAS  Google Scholar 

  • Stauss HM, Godecke A, Mrowka R, et al. (1999) Enhanced blood pressure variability in eNOS knock-out mice. Hypertension 33:1359–1363

    PubMed  CAS  Google Scholar 

  • Stauss HM, Nafz B, Mrowka R, et al. (2000) Blood pressure control in eNOS knock-out mice: comparison with other species under NO blockade. Acta Physiol Scand 168:155–160

    PubMed  CAS  Google Scholar 

  • Stemerman MB (1981) Vascular injury: platelets and smooth muscle cell response. Philos Trans R Soc Lond B Biol Sci 294:217–224

    PubMed  CAS  Google Scholar 

  • Stroes E, Kastelein J, Cosentino F, et al. (1997) Tetrahydrobiopterin restores endothelial function in hypercholesterolemia. J Clin Invest 99:41–46

    PubMed  CAS  Google Scholar 

  • Stuehr D, Pou S, Rosen GM (2001) Oxygen reduction by nitric oxide synthases. J Biol Chem 276:14533–14536

    PubMed  CAS  Google Scholar 

  • Sun D, Huang A, Smith CJ, et al. (1999) Enhanced release of prostaglandins contributes to flow-induced arteriolar dilation in eNOS knockout mice. Circ Res 85:288–293

    PubMed  CAS  Google Scholar 

  • Sun J, Liao JK (2002) Functional interaction of endothelial nitric oxide synthase with a voltage-dependent anion channel. Proc Natl Acad Sci USA 99:13108–13113

    PubMed  CAS  Google Scholar 

  • Taddei S, Virdis A, Mattei P, et al. (1996) Defective L-arginine-nitric oxide pathway in offspring of essential hypertensive patients. Circulation 94:1298–1303

    PubMed  CAS  Google Scholar 

  • Tai SC, Robb GB, Marsden PA (2004) Endothelial nitric oxide synthase: a new paradigm for gene regulation in the injured blood vessel. Arterioscler Thromb Vasc Biol 24:405–412

    PubMed  CAS  Google Scholar 

  • Tiefenbacher CP, Chilian WM, Mitchell M, et al. (1996) Restoration of endothelium-dependent vasodilation after reperfusion injury by tetrahydrobiopterin. Circulation 94:1423–1429

    PubMed  CAS  Google Scholar 

  • Ting HH, Timimi FK, Boles KS, et al. (1996) Vitamin C improves endothelium-dependent vasodilation in patients with non-insulin-dependent diabetes mellitus. J Clin Invest 97:22–28

    PubMed  CAS  Google Scholar 

  • Tracy RP (2002) Diabetes and atherothrombotic disease: linked through inflammation? Semin Vasc Med 2:67–73

    PubMed  Google Scholar 

  • Trovati M, Massucco P, Mattiello L, et al. (1996) The insulin-induced increase of guanosine-3′,5′-cyclic monophosphate in human platelets is mediated by nitric oxide. Diabetes 45:768–770

    PubMed  CAS  Google Scholar 

  • Turrens JF (2003) Mitochondrial formation of reactive oxygen species. J Physiol 552:335–344

    PubMed  CAS  Google Scholar 

  • Uematsu M, Ohara Y, Navas JP, et al. (1995) Regulation of endothelial cell nitric oxide synthase mRNA expression by shear stress. Am J Physiol 269:C1371–C1378

    PubMed  CAS  Google Scholar 

  • Uwabo J, Soma M, Nakayama T, et al. (1998) Association of a variable number of tandem repeats in the endothelial constitutive nitric oxide synthase gene with essential hypertension in Japanese. Am J Hypertens 11:125–128

    PubMed  CAS  Google Scholar 

  • Vallance P, Moncada S (1993) Role of endogenous nitric oxide in septic shock. New Horiz 1:77–86

    PubMed  CAS  Google Scholar 

  • Vallance P, Collier J, Moncada S (1989) Nitric oxide synthesized from L-arginine mediates endothelium-dependent dilatation in human veins in vivo. Cardiovasc Res 23:1053–1057

    PubMed  CAS  Google Scholar 

  • Vallance P, Leone A, Calver A, et al. (1992) Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure. Lancet 339:572–575

    PubMed  CAS  Google Scholar 

  • van der Zee R, Murohara T, Luo Z, et al. (1997) Vascular endothelial growth factor/vascular permeability factor augments nitric oxide release from quiescent rabbit and human vascular endothelium. Circulation 95:1030–1037

    PubMed  Google Scholar 

  • van Geel PP, Pinto YM, Buikema H, et al. (1998) Is the A1166C polymorphism of the angiotensin II type 1 receptor involved in cardiovascular disease? Eur Heart J 19:G13–G17

    PubMed  Google Scholar 

  • Varenne O, Pislaru S, Gillijns H, et al. (1998) Local adenovirus-mediated transfer of human endothelial nitric oxide synthase reduces luminal narrowing after coronary angioplasty in pigs. Circulation 98:919–926

    PubMed  CAS  Google Scholar 

  • Vasquez-Vivar J, Kalyanaraman B, Martasek P, et al. (1998) Superoxide generation by endothelial nitric oxide synthase: the influence of cofactors. Proc Natl Acad Sci USA 95:9220–9225

    PubMed  CAS  Google Scholar 

  • Venema RC, Venema VJ, Ju H, et al. (2003) Novel complexes of guanylate cyclase with heat shock protein 90 and nitric oxide synthase. Am J Physiol 285:H669–H678

    CAS  Google Scholar 

  • Viner RI, Williams TD, Schoneich C (1999) Peroxynitrite modification of protein thiols: oxidation, nitrosylation, and S-glutathiolation of functionally important cysteine residue(s) in the sarcoplasmic reticulum Ca-ATPase. Biochemistry 38:12408–12415

    PubMed  CAS  Google Scholar 

  • Virdis A, Schiffrin EL (2003) Vascular inflammation: a role in vascular disease in hypertension? Curr Opin Nephrol Hypertens 12:181–187

    PubMed  CAS  Google Scholar 

  • Vodovotz Y, Chesler L, Chong H, et al. (1999) Regulation of transforming growth factor β1 by nitric oxide. Cancer Res 59:2142–2149

    PubMed  CAS  Google Scholar 

  • von der Leyen HE, Dzau VJ (2001) Therapeutic potential of nitric oxide synthase gene manipulation. Circulation 103:2760–2765

    PubMed  Google Scholar 

  • Vouldoukis I, Riveros-Moreno V, Dugas B, et al. (1995) The killing of Leishmania major by human macrophages is mediated by nitric oxide induced after ligation of the Fc epsilon RII/CD23 surface antigen. Proc Natl Acad Sci USA 92:7804–7808

    PubMed  CAS  Google Scholar 

  • Wagner AH, Kohler T, Ruckschloss U, et al. (2000a) Improvement of nitric oxide-dependent vasodilatation by HMG-CoA reductase inhibitors through attenuation of endothelial superoxide anion formation. Arterioscler Thromb Vasc Biol 20:61–69

    PubMed  CAS  Google Scholar 

  • Wagner C, Godecke A, Ford M, et al. (2000b) Regulation of renin gene expression in kidneys of eNOS-and nNOS-deficient mice. Pflugers Arch 439:567–572

    PubMed  CAS  Google Scholar 

  • Walker G, Pfeilshifter J, Kunz D (1997) Mechanisms of suppression of inducible nitric oxide synthase (iNOS) expression in interferon (IFN)-γ-stimulated RAW 264.7 cells by dexamethasone. Evidence for glucocorticoid-induced degradation of iNOS protein by calpain as a key step in post-transcriptional regulation. J Biol Chem 272:16679–16687

    PubMed  CAS  Google Scholar 

  • Wallerath T, Gath I, Aulitzky WE, et al. (1997) Identification of the NO synthase isoforms expressed in human neutrophil granulocytes, megakaryocytes and platelets. Thromb Haemost 77:163–167

    PubMed  CAS  Google Scholar 

  • Wang X, Wang J, Trudinger B (2003) Gene expression of nitric oxide synthase by human umbilical vein endothelial cells: the effect of fetal plasma from pregnancy with umbilical placental vascular disease. Br J Obstet Gynaecol 110:53–58

    CAS  Google Scholar 

  • Wang XL, Wang J (2000) Endothelial nitric oxide synthase gene sequence variations and vascular disease. Mol Genet Metab 70:241–251

    PubMed  CAS  Google Scholar 

  • Wattanapitayakul SK, Mihm MJ, Young AP, et al. (2001) Therapeutic implications of human endothelial nitric oxide synthase gene polymorphism. Trends Pharmacol Sci 22:361–368

    PubMed  CAS  Google Scholar 

  • Wedgwood S, Mitchell CJ, Fineman JR, et al. (2003) Developmental differences in the shear stress-induced expression of endothelial NO synthase: changing role of AP-1. Am J Physiol Lung Cell Mol Physiol 284:L650–L662

    PubMed  CAS  Google Scholar 

  • Wei CC, Wang ZQ, Meade AL, et al. (2002) Why do nitric oxide synthases use tetrahydrobiopterin? J Inorg Biochem 91:6618–6624

    Google Scholar 

  • Weiner CP, Lizasoain I, Baylis SA, et al. (1994) Induction of calcium-dependent nitric oxide synthases by sex hormones. Proc Natl Acad Sci USA 91:5212–5216

    PubMed  CAS  Google Scholar 

  • Werner ER, Gorren AC, Heller R, et al. (2003) Tetrahydrobiopterin and nitric oxide: mechanistic and pharmacological aspects. Exp Biol Med 228:1291–1302

    CAS  Google Scholar 

  • White KA, Marletta MA (1992) Nitric oxide synthase is a cytochrome P-450 type hemoprotein. Biochemistry 31:6627–6631

    PubMed  CAS  Google Scholar 

  • Whittle BJR (1997) Nitric oxide—a mediator of inflammation or mucosal defence. Eur J Gastroenterol Hepatol 9:1026–1032

    PubMed  CAS  Google Scholar 

  • Wilcox JN, Subramanian RR, Sundell CL, et al. (1997) Expression of multiple isoforms of nitric oxide synthase in normal and atherosclerotic vessels. Arterioscler Thromb Vasc Biol 17:2479–2488

    PubMed  CAS  Google Scholar 

  • Xie QW, Cho HJ, Calaycay J, et al. (1992) Cloning and characterization of inducible nitric oxide synthase from mouse macrophages. Science 256:225–228

    PubMed  CAS  Google Scholar 

  • Xu HL, Galea E, Santizo RA, et al. (2001) The key role of caveolin-1 in estrogen-mediated regulation of endothelial nitric oxide synthase function in cerebral arterioles in vivo. J Cereb Blood Flow Metab 21:907–913

    PubMed  CAS  Google Scholar 

  • Xu KY, Huso DL, Dawson TM, et al. (1999) Nitric oxide synthase in cardiac sarcoplasmic reticulum. Proc Natl Acad Sci USA 96:657–662

    PubMed  CAS  Google Scholar 

  • Xu L, Eu JP, Meissner G, et al. (1998) Activation of the cardiac calcium release channel (ryanodine receptor) by poly-S-nitrosylation. Science 279:234–237

    PubMed  CAS  Google Scholar 

  • Yang Y, Loscalzo J (2005) S-nitrosoprotein formation and localization in endothelial cells. Proc Natl Acad Sci USA 102:117–122

    PubMed  CAS  Google Scholar 

  • Yeh DC, Duncan JA, Yamashita S, et al. (1999) Depalmitoylation of endothelial nitric oxide synthase by acyl-protein thioesterase 1 is potentiated by Ca2+-calmodulin. J Biol Chem 274:33148–33154

    PubMed  CAS  Google Scholar 

  • Zabel U, Kleinschnitz C, Oh P, et al. (2002) Calcium-dependent membrane association sensitizes soluble guanylyl cyclase to nitric oxide. Nat Cell Biol 4:307–311

    PubMed  CAS  Google Scholar 

  • Zembowicz A, Tang JL, Wu KK (1995) Transcriptional induction of endothelial nitric oxide synthase type III by lysophosphatidylcholine. J Biol Chem 270:17006–17010

    PubMed  CAS  Google Scholar 

  • Zhang R, Min W, Sessa WC (1995) Functional analysis of the human endothelial nitric oxide synthase promoter. Sp1 and GATA factors are necessary for basal transcription in endothelial cells. J Biol Chem 270:15320–15326

    PubMed  CAS  Google Scholar 

  • Zhao G, Bernstein RD, Hintze TH (1999) Nitric oxide and oxygen utilization: exercise, heart failure and diabetes. Coron Artery Dis 10:315–320

    PubMed  CAS  Google Scholar 

  • Zhao YY, Liu Y, Stan RV, et al. (2002) Defects in caveolin-1 cause dilated cardiomyopathy and pulmonary hypertension in knockout mice. Proc Natl Acad Sci USA 99:11375–11380

    PubMed  CAS  Google Scholar 

  • Ziche M, Morbidelli L (2000) Nitric oxide and angiogenesis. J Neurooncol 50:139–148

    PubMed  CAS  Google Scholar 

  • Ziche M, Morbidelli L, Masini E, et al. (1994) Nitric oxide mediates angiogenesis in vivo and endothelial cell growth and migration in vitro promoted by substance P. J Clin Invest 94:2036–2044

    PubMed  CAS  Google Scholar 

  • Ziche M, Morbidelli L, Choudhuri R, et al. (1997) Nitric oxide synthase lies downstream from vascular endothelial growth factor-induced but not basic fibroblast growth factor-induced angiogenesis. J Clin Invest 99:2625–2634

    PubMed  CAS  Google Scholar 

  • Ziegler T, Silacci P, Harrison VJ, et al. (1998) Nitric oxide synthase expression in endothelial cells exposed to mechanical forces. Hypertension 32:351–355

    PubMed  CAS  Google Scholar 

  • Zimmermann K, Optiz N, Dedio J, et al. (2002) NOSTRIN: a protein modulating nitric oxide release and subcellular distribution of endothelial nitric oxide synthase. Proc Natl Acad Sci USA 99:17167–17172

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to S. Moncada .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2006 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Moncada, S., Higgs, E.A. (2006). Nitric Oxide and the Vascular Endothelium. In: Moncada, S., Higgs, A. (eds) The Vascular Endothelium I. Handbook of Experimental Pharmacology, vol 176/I. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-32967-6_7

Download citation

Publish with us

Policies and ethics