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Nitric Oxide in Atherosclerosis

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Nitric Oxide and the Cardiovascular System

Part of the book series: Contemporary Cardiology ((CONCARD))

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Abstract

The importance of nitric oxide (NO·) in the regulation of vascular physiology and the pathophysiology of vascular diseases is now widely recognized. The discovery of NO· as a key molecule released by the endothelium to control vascular homeostasis stems from the finding of Furchgott and Zawadzki that an intact vascular endothelium is required for a vasodilator response to muscarinic agonists. These investigators found that in the presence of an intact endothelium, acetylcholine produces dose-dependent relaxation in isolated arterial segments by triggering the release of a potent vasodilator substance termed endothelium-derived relaxing factor (1). In contrast, when the endothelium is denuded, acetylcholine produces contraction owing to unopposed direct vasoconstrictor effects on vascular smooth muscle (1). Endothelium-derived relaxing factor (EDRF) was eventually identified as NO·, as both possess similar chemical and biological properties (2,3). The specific identity of EDRF has not been without controversy as it has been suggested that an S-nitrosated compound, S-nitroso-L-cysteine, is a more likely candidate molecule (4).

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References

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

    Article  PubMed  CAS  Google Scholar 

  2. Ignarro LJ, Byrns RE, Buga GM, Wood KS. Endothelium-derived relaxing factor from pulmonary artery and vein possess pharmacologic and chemical properties identical to those of nitric oxide radical. Circ Res 1987; 61: 866–879.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  4. Myers PR, Minor RL, Guerra R, Bates JN, Harrison DG. Vasorelaxant properties of the endothelium-derived relaxing factor more closely resembles S-nitrosocysteine than nitric oxide. Nature 1990; 345: 161–163.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  6. Loscalzo J, Welch G. Nitric oxide and its role in the cardiovascular system. Progr Cardiovasc Dis 1995; 38: 87–104.

    Article  CAS  Google Scholar 

  7. Stamler JS, Singel DJ, Loscalzo J. Biochemistry of nitric oxide and its redox-activated forms. Science 1992; 258: 1898–1902.

    Article  PubMed  CAS  Google Scholar 

  8. Stamler J, Simon DI, Osborne JA, Mullins ME, Jaraki O, Michel T, et al. S-nitrosylation of proteins with nitric oxide: synthesis and characterization of biologically active compounds. Proc Natl Acad Sci USA 1992; 89: 444–448.

    Article  PubMed  CAS  Google Scholar 

  9. Najibi S, Cohen RA. Enhanced role of K+ channels in relaxation of hypercholesterolemic rabbit carotid artery to NO. Am J Physiol 1995; 269: H805 - H811.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  11. Vallance P, Collier J, Moncada S. Effects of endothelium-derived nitric oxide on peripheral arteriolar tone in man. Lancet 1989; 2: 997–1000.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  13. Busse R, Mülsch A, Fleming I, Hecker M. Mechanisms of nitric oxide release from the vascular endothelium. Circulation 1993; 87: V18 - V25.

    CAS  Google Scholar 

  14. Cooke JP, Tsao PS. Is NO an endogenous antiatherogenic molecule? Arterioscler Thromb 1994; 14: 653–655.

    Article  PubMed  CAS  Google Scholar 

  15. Chester AH, O’Neil GS, Moncada S, Tadjkarimi S, Yacoub MH. Low basal and stimulated release of nitric oxide in atherosclerotic epicardial coronary arteries. Lancet 1990; 336: 897–900.

    Article  PubMed  CAS  Google Scholar 

  16. Lefroy DC, Crake T, Uren NG, Davies GJ, Maseri A. Effect of inhibition of nitric oxide synthesis on epicardial coronary artery caliber and coronary blood flow in humans. Circulation 1993; 88: 43–54.

    Article  PubMed  CAS  Google Scholar 

  17. Kelm M, Schrader J. Control of coronary vascular tone by nitric oxide. Circ Res 1990; 66: 1561–1575.

    Article  PubMed  CAS  Google Scholar 

  18. Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990’s. Nature 1993; 362: 801–808.

    Article  PubMed  CAS  Google Scholar 

  19. Ware JA, Heistad DD. Seminars in medicine of the Beth Israel Hospital, Boston. Platelet-endothelium interactions. N Engl J Med 1993; 328: 628–635.

    Article  PubMed  CAS  Google Scholar 

  20. Mellion BT, Ignarro LJ, Ohlstein EH, Pontecorvo EG, Hyman AL, Kadowitz PJ. Evidence for the inhibitory role of guanosine 3’, 5’-monophosate in ADP-induced human platelet aggregation in the presence of nitric oxide and related vasodilators. Blood 1981; 57: 946–955.

    PubMed  CAS  Google Scholar 

  21. Mendelsohn ME, O’Neill S, George D, Loscalzo J. Inhibition of fibrinogen binding to human platelets by S-nitroso-N-acetylcysteine. J Biol Chem 1990;265:19, 028–19, 034.

    Google Scholar 

  22. Michelson AD, Benoit SE, Furman MI, Breckwoldt WL, Rohrer MJ, Barnard MR, et al. Effects of nitric oxide/EDRF on platelet surface glycoproteins. Am J Physiol 1996; 270: H1640 - H1648.

    PubMed  CAS  Google Scholar 

  23. Radomski MW, Palmer RM, Moncada S. Endogenous nitric oxide inhibits human platelet adhesion to vascular endothelium. Lancet 1987; 2: 1057, 1058.

    Google Scholar 

  24. Sneddon JM, Vane JR. Endothelium-derived relaxing factor reduces platelet adhesion to bovine endothelial cells. Proc Natl Acad Sci USA 1988; 85: 2800–2804.

    Article  PubMed  CAS  Google Scholar 

  25. Yao SK, Ober JC, Krishnaswami A, Ferguson JJ, Anderson HV, Golino P, et al. Endogenous nitric oxide protects against platelet aggregation and cyclic flow variations in stenosed and endothelium-injured arteries. Circulation 1992; 86: 1302–1309.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  27. Vasta, V, Meacci, E, Farnararo, M, Bruni, P. Identification of a specific transport system for L-arginine in human platelets. Biochem Biophys Res Commun 1995; 206: 878–884.

    Article  PubMed  CAS  Google Scholar 

  28. Freedman JE, Loscalzo J, Barnard MR, Alpert C, Keaney JF Jr, Michelson AD. Nitric oxide released from activated platelets inhibits platelet recruitment. J Clin Invest 1997; 100: 350–356.

    Article  PubMed  CAS  Google Scholar 

  29. Gimbrone MA Jr. Vascular endothelium: an integrator of pathophysiologic stimuli in atherosclerosis. Am J Cardiol 1995; 75: 67B - 70B.

    Article  PubMed  CAS  Google Scholar 

  30. Bath PM, Hassall DG, Gladwin AM, Palmer RM, Martin JF. Nitric oxide and prostacyclin. Divergence of inhibitory effects on monocyte chemotaxis and adhesion to endothelium in vitro. Arteroscler Thromb 1991; 11: 254–260.

    CAS  Google Scholar 

  31. Tsao PS, Lewis NP, Alpert S, Cooke JP. Exposure to shear stress alters endothelial adhesiveness. Role of nitric oxide. Circulation 1995; 92: 3513–3519.

    Article  PubMed  CAS  Google Scholar 

  32. Ma X, Weyrich AS, Lefer DJ, Lefer AM. Diminished basal nitric oxide release after myocardial ischemia and reperfusion promotes neutrophil adherence to coronary endothelium. Circ Res 1993; 72: 403–412.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  34. Tsao PS, Buitrago R, Chan JR, Cooke JP. Fluid flow inhibits endothelial adhesiveness. Nitric oxide and transcriptional regulation of VCAM-1. Circulation 1996; 94: 1682–1689.

    Article  PubMed  CAS  Google Scholar 

  35. Lefer DJ, Klunk DA, Lutty GA, Merges C, Schleimer RP, Bochner BS, et al. Nitric oxide donors reduce basal ICAM-1 expression on human aortic endothelial cells. Circulation 1993; 88: I - 565.

    Google Scholar 

  36. Adams MR, Jessup W, Hailstones D, Celermajer DS. L-arginine reduces human monocyte adhesion to vascular endothelium and endothelial expression of cell adhesion molecules. Circulation 1997; 95: 662–668.

    Article  PubMed  CAS  Google Scholar 

  37. Zeiher AM, Fisslthaler B, Schray-Utz B, Busse R. Nitric oxide modulates the expression of monocyte chemoattractant protein 1 in cultured human endothelial cells. Circ Res 1995; 76: 980–986.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  39. Guo K, Andres V, Walsh K. Nitric oxide-induced downregulation of cdk2 activity and cyclin A gene transcription in vascular smooth muscle cells. Circulation 1998; 97: 2066–2072.

    Article  PubMed  CAS  Google Scholar 

  40. Rizvi MA, Myers PR. Nitric oxide modulates basal and endothelin-induced coronary artery vascular smooth muscle cell proliferation and collagen levels. J Mol Cell Cardiol 1997; 29: 1779–1789.

    Article  PubMed  CAS  Google Scholar 

  41. Sarkar R, Meinberg EG, Stanley JC, Gordon D, Webb RC. Nitric oxide reversibly inhibits the migration of cultured vascular smooth muscle cells. Circ Res 1996; 78: 225–230.

    Article  PubMed  CAS  Google Scholar 

  42. Scott-Burden T, Vanhoutte PM. The endothelium as a regulator of vascular smooth muscle cell proliferation. Circulation 1993; 87: V51 - V55.

    Google Scholar 

  43. Busse R, Mülsch A. Induction of nitric oxide synthase by cytokines in vascular smooth muscle cells. FEBS Lett 1990; 275: 87–90.

    Article  PubMed  CAS  Google Scholar 

  44. Scott-Burden T, Schini VB, Elizondo E, Junquero DC, Vanhoutte PM. Platelet-derived growth factor suppresses and fibroblast growth factor enhances cytokine-induced production of nitric oxide by cultured smooth muscle cells. Circ Res 1992; 71: 1088–1100.

    Article  PubMed  CAS  Google Scholar 

  45. Lawson DL, Mehta JL, Nichols WW, Mehta P, Donnelly WH. Superoxide radical-mediated endothelial injury and vasoconstriction of rat thoracic aortic rings. J Lab Clin Med 1990; 115: 541–548.

    PubMed  CAS  Google Scholar 

  46. Keaney JF Jr, Vita JA. Atherosclerosis, oxidative stress and antioxidant protection in endothelium-derived relaxng factor action. Prog Cardiovasc Dis 1995; 38: 129–154.

    Article  PubMed  Google Scholar 

  47. Ohara Y, Peterson TE, Harrison DG. Hypercholesterolemia increases endothelial superoxide anion production. J Clin Invest 1993; 91: 2546–2551.

    Article  PubMed  CAS  Google Scholar 

  48. Moro MA, Darley-Usmar VM, Goodwin DA, Read NG, Zamora-Pino R, Feelisch M, et al. Paradoxical fate and biological action of peroxynitrite on human platelets. Proc Natl Acad Sci USA 1994; 91: 6702–6706.

    Article  PubMed  CAS  Google Scholar 

  49. Villa LM, Salas E, Darley-Usmar VM, Radomski MW, Moncada S. Peroxynitrite induces both vasodilation and impaired vascular relaxation in the isolated perfused rat heart. Proc Natl Acad Sci USA 1994; 91:12, 383–12, 387.

    Google Scholar 

  50. Hogg N, Kalyanaraman B, Joseph J, Struck A, Parthasarathy S. Inhibition of low-density lipoprotein oxidation by nitric oxide: potential role in atherogenesis. FEBS Lett 1993; 334: 170–174.

    Article  PubMed  CAS  Google Scholar 

  51. Cardona-Sanclemente LE, Born GV. Effect of inhibition of nitric oxide synthesis on the uptake of LDL and fibrinogen by arterial walls and other organs of the rat. Br J Pharmacol 1995; 114: 1490–1494.

    Article  PubMed  CAS  Google Scholar 

  52. Chang GJ, Woo P, Honda HM, Ignarro LJ, Young L, Berliner JA, et al. Oxidation of LDL to a biologically active form by derivatives of nitric oxide and nitrite in the absence of superoxide. Arterioscler Thromb 1994; 14: 1808–1814.

    Article  PubMed  CAS  Google Scholar 

  53. Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA. Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci USA 1990; 87: 1620–1624.

    Article  PubMed  CAS  Google Scholar 

  54. Weyer RMF, Löscher TF, Cosentino F, Rabelink TJ. Atherosclerosis and the two faces of endothelial nitric oxide synthase. Circulation 1998; 97: 108–112.

    Article  Google Scholar 

  55. Bjorkerud S, Bjorkerud B. Apoptosis is abundant in human atherosclerotic lesions, especially in inflammatory cells (macrophages and T cells), and may contribute to the accumulation of gruel and plaque instability. Am J Pathol 1996; 149: 367–380.

    PubMed  CAS  Google Scholar 

  56. Geng YJ, Henderson LE, Levesque EB, Muszynski M, Libby P. Fas is expressed in human atherosclerotic intima and promotes apoptosis of cytokine-primed human vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 1997; 17: 2200–2208.

    Article  PubMed  CAS  Google Scholar 

  57. Hegyi L, Skepper JN, Cary NR, Mitchinson MJ. Foam cell apoptosis and the development of the lipid core of human atherosclerosis. J Pathol 1996; 180: 423–429.

    Article  PubMed  CAS  Google Scholar 

  58. Fukuo K, Inoue T, Morimoto S, Nakahashi T, Yasuda O, Kitano S, et al. Nitric oxide mediates cytotoxity and basic fibroblast growth factor release in culutred vascular smooth muscle cells. A possible mechanism of neovascularization in atherosclerotic plaques. J Clin Invest 1995; 95: 669–676.

    Article  PubMed  CAS  Google Scholar 

  59. Fukuo K, Nakahashi T, Nomura S, Hata S, Suhara T, Shimizu M, et al. Possible participation of Fasmediated apoptosis in the mechanism of atherosclerosis. Gerontology 1997; 43: 35–42.

    Article  PubMed  CAS  Google Scholar 

  60. Shimaoka M, Iida T, Ohara A, Taenaka N, Mashimo T, Honda T, et al. NOC, a nitric-oxide-releasing compound, induces dose dependent apoptosis in macrophages. Biochem Biophys Res Commun 1995; 209: 519–526.

    Article  PubMed  CAS  Google Scholar 

  61. Yang X, Galeano NF, Szabolcs M, Sciacca RR, Cannon PJ. Oxidized low density lipoproteins alter macrophage lipid uptake, apootosis, viability and nitric oxide synthesis. J Nutr 1996; 126: 1072S - 1075S.

    PubMed  CAS  Google Scholar 

  62. Verbeuren TJ, Jordaens FH, Zonnekeyn LL, Van Hove CE, Coene MC, Herman AG. Effect of hypercholesterolemia on vascular reactivity in the rabbit. I. Endothelium-dependent and endothelium-independent contractions and relaxations in isolated arteries of control and hypercholesterolemic rabbits. Circ Res 1986; 58: 552–564.

    Article  PubMed  CAS  Google Scholar 

  63. Bossaller C, Habib GB, Yamamoto H, Williams C, Wells S, Henry PD. Impaired muscarinic endothelium-dependent relaxation and cyclic guanosine 5’-monophosphate formation in atherosclerotic human coronary artery and rabbit aorta. J Clin Invest 1987; 79: 170–174.

    Article  PubMed  CAS  Google Scholar 

  64. Freiman PC, Mitchell GC, Heistad DD, Armstrong ML, Harrison DG. Atherosclerosis impairs endothelium-dependent vascular relaxation to acetylcholine and thrombin in primates. Circ Res 1986; 58: 783–789.

    Article  PubMed  CAS  Google Scholar 

  65. Cohen RA, Zitnay KM, Haudenschild CC, Cunningham LD. Loss of selective endothelial cell vaso-active functions caused by hypercholesterolemia in pig coronary arteries. Circ Res 1988; 63: 903–910.

    Article  PubMed  CAS  Google Scholar 

  66. Ludmer PL, Selwyn AP, Shook TL, Wayne RR, Mudge GH, Alexander RW, et al. Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries. N Engl J Med 1986; 315: 1046–1051.

    Article  PubMed  CAS  Google Scholar 

  67. Anderson TJ, Gerhard MD, Meredith IT, Charbonneau F, Delagrange D, Creager MA, et al. Systemic nature of endothelial dysfunction in atherosclerosis. Am J Cardiol 1995; 75: 71B - 74B.

    Article  PubMed  CAS  Google Scholar 

  68. McLenachan JM, Williams JK, Fish RD, Ganz P, Selwyn AP. Loss of flow-mediated endothelium-dependent dilation occurs early in the development of atherosclerosis. Circulation 1991; 84: 1273–1278.

    Article  PubMed  CAS  Google Scholar 

  69. Vita JA, Treasure CB, Nabel EG, McLenachan JM, Fish RD, Yeung AC, et al. Coronary vasomotor response to acetylcholine relates to risk factors for coronary artery disease. Circulation 1990; 81: 491–497.

    Article  PubMed  CAS  Google Scholar 

  70. Reddy KG, Nair R, Sheehan HM, Hodgson JM. 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 1994; 23: 833–843.

    Article  PubMed  CAS  Google Scholar 

  71. Otsuji S, Nakajima O, Waku S, Kojima S, Hosokawa H, Kinoshita I, et al. Attenuation of acetylcholine-induced vasoconstriction by L-arginine is related to the progression of atherosclerosis. Am Heart J 1995; 129: 1094–1100.

    Article  PubMed  CAS  Google Scholar 

  72. Osborne JA, Siegman MJ, Sedar AW, Mooers SU, Lefer AM. Lack of endothelium-dependent relaxation in coronary resistance arteries of cholesterol-fed rabbits. Cell Physiol 1989; 25: C591–0597.

    Google Scholar 

  73. Yaghoubi M, Cayatte AJ, Cohen RA. Decreased nitric oxide response precedes impaired endothelium-dependent relaxation of hypercholesterolemic ApoE knockout mouse aorta. Circulation 1998; 98: I44.

    Google Scholar 

  74. Verbeuren TJ, Jordaens FH, Van Hove CE, Van Hoydonck AE, Herman AG. Release and vascular activity of endothelium-derived relaxing factor in atherosclerotic rabbit aorta. Eur J Pharmacol 1990; 191: 173–184.

    Article  PubMed  CAS  Google Scholar 

  75. Böger RH, Bode-Böger SM, Miigge A, Kienke S, Brandes R, Dwenger A, et al. Supplementation of hypercholesterolaemic rabbits with L-arginine reduces the vascular release of superoxide anions and restores NO production. Atherosclerosis 1995; 117: 273–284.

    Article  PubMed  Google Scholar 

  76. Durante W, Liao L, Schafer AI. Differential regulation of L-arginine transport and inducible NOS in cultured vascular smooth muscle cells. Am J Physiol 1995; 268: H1158 - H1164.

    PubMed  CAS  Google Scholar 

  77. Arnal JF, Munzel T, Venema RC, James NL, Bai CL, Mitch WE, et al. Interactions between L-arginine and L-glutamine change endothelial NO production: an effect independent of NO synthase substrate availability. J Clin Invest 1995; 99: 433–438.

    Google Scholar 

  78. Bode-Böger SM, Böger RH, Kienke S, Junker W, Frölich JC. Elevated L-arginine/dimethylarginine ratio contributes to enhanced systemic NO production by dietary L-arginine in hypercholesterolemic rabbits. Biochem Biophys Res Commun 1996; 219: 598–603.

    Article  PubMed  Google Scholar 

  79. Liao JK, Shin WS, Lee WY, Clark SL. Oxidized low-density lipoprotein decreases the expression of endothelial nitric oxide synthase. J Biol Chem 1995; 270: 319–324.

    Article  PubMed  CAS  Google Scholar 

  80. Gryglewski RJ, Palmer RM, Moncada S. Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor. Nature 1986; 320: 454–456.

    Article  PubMed  CAS  Google Scholar 

  81. Mügge A, Elwell JH, Peterson TE, Hofemeyer TG, Heistad DD, Harrison DG. Chronic treatment with polyethylene glycolated superoxide dismutase partially restores endothelium-dependent vascular relaxations in cholesterol-fed rabbits. Circ Res 1991; 69: 1293–1300.

    Article  PubMed  Google Scholar 

  82. Keaney JF Jr, Gaziano JM, Xu A, Frei B, Curran-Cellentano J, Shwaery GT, et al. Dietary antioxidants preserve endothelium-dependent vessel relaxation in cholesterol-fed rabbits. Proc Natl Acad Sci USA 1993;90:11, 880–11, 884.

    Google Scholar 

  83. Lapenna D, de Gioia S, Ciofani G, Mezzetti A, Ucchino S, Calafiore AM, et al. Glutathione-related antioxidant defenses in human atherosclerotic plaques. Circulation 1998; 97: 1930–1934.

    Article  PubMed  CAS  Google Scholar 

  84. Minor RL, Meyers PR, Guerra R Jr, Bates JN, Harrison DG. Diet-induced atherosclerosis increases the release of nitrogen oxides from rabbit aorta. J Clin Invest 1990; 86: 2109–2116.

    Article  PubMed  CAS  Google Scholar 

  85. Clancy RM, Leszcynska-Piziak J, Abramson SB. Nitric oxide, an endothelial cell relaxation factor, inhibits neutrophil superoxide anion production via a direct action on the NADPH oxidase. J Clin Invest 1992; 90: 1116–1121.

    Article  PubMed  CAS  Google Scholar 

  86. Rajagopalan S, Kurz S, Munzel T, Tarpey M, Freeman BA, Griendling KL, et al. Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/ NADPH oxidase activation. Contribution to alteration of vasomotor tone. J Clin Invest 1996; 97: 1916–1923.

    Article  PubMed  CAS  Google Scholar 

  87. Pritchard KA, Groszek L, Smalley DM, Sessa WC, Wu M, Villalon P, et al. Native low density lipoprotein increases endothelial cell nitric oxide synthase generation of superoxide anion. Circ Res 1995; 77: 510–518.

    Article  PubMed  CAS  Google Scholar 

  88. Tsao PS, Theilmeier G, Singer AH, Leung LL, Cooke JP. L-arginine attenuates platelet reactivity in hypercholesterolemic rabbits. Arterioscler Thromb 1994; 14: 1529–1533.

    Article  PubMed  CAS  Google Scholar 

  89. Lefer AM, Ma X. Decreased basal nitric oxide release in hypercholesterolemia increases neutrophil adherence to rabbit coronary artery endothelium. Arterioscler Thromb 1993; 13: 771–776.

    Article  PubMed  CAS  Google Scholar 

  90. Tsao PS, McEvoy LM, Drexler H, Butcher EC, Cooke JP. Enhanced endothelial adhesiveness in hypercholesterolemia is attenuated by L-arginine. Circulation 1994; 89: 2176–2182.

    Article  PubMed  CAS  Google Scholar 

  91. Adams MR, McCredie R, Jessup W, Rodinson J, Sullivan D, Celermajer DS. Oral L-arginine improves endothelium-dependent dilatation and reduces monocyte adhesion to endothelial cells in young men with coronary artery disease. Atherosclerosis 1997; 129: 261–269.

    Article  PubMed  CAS  Google Scholar 

  92. Chin JH, Azhar S, Hoffman BB. Inactivation of endothelium derived relaxing factor by oxidized lipoproteins. J Clin Invest 1992; 89: 10–18.

    Article  PubMed  CAS  Google Scholar 

  93. Koglin J, Glysing-Jensen T, Mudgett JS, Russell ME. Exacerbated transplant arteriosclerosis in inducible nitric oxide-deficient mice. Circulation 1998; 97: 2059–2065.

    Article  PubMed  CAS  Google Scholar 

  94. Meredith IT, Yeung AC, Weidinger FF, Anderson TJ, Uehata A, Ryan TJ, et al. Role of impaired endothelium-dependent vasodilation in ischemic manifestations of coronary artery disease. Circulation 1993; 87: V56 - V66.

    Google Scholar 

  95. Cox DA, Vita JA, Treasure CB, Fish RD, Alexander RW, Ganz P, et al. Impairment of flow-mediated coronary dilation by atherosclerosis in man. Circulation 1989; 80: 458–465.

    Article  PubMed  CAS  Google Scholar 

  96. Nabel EG, Selwyn AP, Ganz P. Large coronary arteries in humans are responsive to changing blood flow: an endothelium-dependent mechanism that fails in patients with atherosclerosis. J Am Coll Cardiol 1990; 16: 349–356.

    Article  PubMed  CAS  Google Scholar 

  97. Gordon JB, Ganz P, Nabel EG, Fish RD, Zebede J, Mudge GH, et al. Atherosclerosis influences the vasomotor response of epicardial coronary arteries to exercise. J Clin Invest 1989; 83: 1946–1952.

    Article  PubMed  CAS  Google Scholar 

  98. Yeung AC, Vekshtein VI, Krantz DS, Vita JA, Ryan TJ Jr, Ganz P, et al. The effect of atherosclerosis on the vasomotor response of coronary arteries to mental stress. N Engl J Med 1991; 325: 1551–1556.

    Article  PubMed  CAS  Google Scholar 

  99. Zeiher AM, Drexler H, Wollschlager H, Just H. Endothelial dysfunction of the coronary microvasculature is associated with impaired coronary blood flow regulation in patients with early atherosclerosis. Circulation 1991; 84: 1984–1992.

    Article  PubMed  CAS  Google Scholar 

  100. Quyyumi AA, Dakak N, Andrews NP, Gilligan DM, Panza JA, Cannon RO 3rd. Contribution of nitric oxide to metabolic coronary vasodilation in the human heart. Circulation 1995; 92: 320–326.

    Article  PubMed  CAS  Google Scholar 

  101. Yao SK, Akhtar S, Scott-Burden T, Ober JC, Golino P, Buja LM, et al. Endogenous and exogenous nitric oxide protect against intracoronary thrombosis and reocclusion after thrombolysis. Circulation 1995; 92: 1005–1010.

    Article  PubMed  CAS  Google Scholar 

  102. Adrie C, Bloch KD, Moreno PR, Hurford WE, Guerrero JL, Holt R, et al. Inhaled nitric oxide increases coronary artery patency after thrombolysis. Circulation 1996; 94: 1919–1926.

    Article  PubMed  CAS  Google Scholar 

  103. Girerd XJ, Hirsch AT, Cooke JP, Dzau VJ, Creager MA. L-arginine augments endothelium-dependent vasodilation in cholesterol-fed rabbits. Circ Res 1990; 67: 1301–1308.

    Article  PubMed  CAS  Google Scholar 

  104. Mügge A, Harrison DG. L-arginine does not restore endothelial dysfunction in atherosclerotic rabbit aorta in vitro. Blood Vessels 1991; 28: 354–357.

    PubMed  Google Scholar 

  105. Cooke JP, Andon NA, Girerd XJ, Hirsch AT, Creager MA. Arginine restores cholinergic relaxation of hypercholesterolemic rabbit thoracic aorta. Circulation 1991; 83: 1057–1062.

    Article  PubMed  CAS  Google Scholar 

  106. Cooke JP, Singer AH, Tsao P, Zera P, Rowan RA, Bellingham ME. Antiatherogenic effects of Larginine in the hypercholesterolemic rabbit. J Clin Invest 1992; 90: 1168–1172.

    Article  PubMed  CAS  Google Scholar 

  107. Wang BY, Singer AH, Tsao PS, Drexler H, Kosek J, Cooke JP. Dietary arginine prevents atherogenesis in the coronary artery of the hypercholesterolemic rabbit. J Am Coll Cardiol 1994; 23: 452–458.

    Article  PubMed  CAS  Google Scholar 

  108. Singer AH, Tsao PS, Wang BY, Bloch DA, Cooke JP. Discordant effects of dietary L-arginine on vascular structure and reactivity in hypercholesterolemic rabbits. J Cardiovasc Pharmacol 1995; 25: 710–716.

    Article  PubMed  CAS  Google Scholar 

  109. Candipan RC, Wang B, Buitrago R, Tsao PS, Cooke JP. Regression or progression. Dependency on vascular nitric oxide. Arterioscler Thromb Vasc Biol 1996; 16: 44–50.

    Article  PubMed  CAS  Google Scholar 

  110. Böger RH, Bode-Böger SM, Brandes RP, Phivthong-ngam L, Bohme M, Nafe R, et al. Dietary Larginine reduces the progression of atherosclerosis in cholesterol-fed rabbits: comparison with lovastatin. Circulation 1997; 96: 1282–1290.

    Article  PubMed  Google Scholar 

  111. Cayatte AJ, Palacino JJ, Horten K, Cohen RA. Chronic inhibition of nitric oxide production accelerates neointimal formation and impairs endothelial function in hypercholesterolemic rabbits. Arterioscler Thromb 1994; 14: 753–759.

    Article  PubMed  CAS  Google Scholar 

  112. Naruse K, Shimizu K, Muramatsu M, Told Y, Miyazaki Y, Okumura K, et al. Long-term inhibition of NO synthesis promotes atherosclerosis in the hypercholesterolemic rabbit thoracic aorta. PGH2 does not contribute to impaired endothelium-dependent relaxation. Arterioscler Thromb 1994; 14: 746–752.

    Article  PubMed  CAS  Google Scholar 

  113. Buttery LD, Springall DR, Chester AH, Evans TJ, Standfield N, Parums DV, et al. Inducible nitric oxide synthase is present within human atherosclerotic lesions and promotes the formation and activity of peroxynitrite. Lab Invest 1996; 75: 77–85.

    PubMed  CAS  Google Scholar 

  114. Ravalli S, Albala A, Ming M, Szabolcs M, Barbone A, Michler RE, et al. Inducible nitric oxide synthase expression in smooth muscle cells and macrophages of human transplant coronary artery disease. Circulation 1998; 97: 2338–2345.

    Article  PubMed  CAS  Google Scholar 

  115. Weidinger FF, McLenachan JM, Cybulsky MI, Jordan JB, Rennke HG, Hollenberg NK, et al. Persistent dysfunction of regenerated endothelium after balloon angioplasty of rabbit iliac artery. Circulation 1990; 81: 1667–1679.

    Article  PubMed  CAS  Google Scholar 

  116. Tarry WC, Makhoul RG. L-arginine improves endothelium-dependent vasorelaxation and reduces intimal hyperplasia after balloon angioplasty. Arterioscler Thromb 1994; 14: 938–943.

    Article  PubMed  CAS  Google Scholar 

  117. Hamon M, Vallet B, Bauters C, Wernert N, McFadden EP, Lablanche JM, et al. Long-term oral administration of L-arginine reduces intimai thickening and enhances neoendothelium-dependent acetycholine-induced relaxation after arterial injury. Circulation 1994; 90: 1357–1362.

    Article  PubMed  CAS  Google Scholar 

  118. Groves PH, Banning AP, Penny WJ, Newby AC, Cheadle HA, Lewis MJ. The effects of exogenous nitric oxide on smooth muscle cell proliferation following porcine carotid angioplasty. Cardiovasc Res 1995; 30: 87–96.

    PubMed  CAS  Google Scholar 

  119. Marks DS, Vita JA, Folts JD, Keaney JF Jr, Welch GN, Loscalzo J. Inhibition of neointimal proliferation in rabbits after vascular injury by a single treatment with a protein adduct of nitric oxide. J Clin Invest 1995; 96: 2630–2638.

    Article  PubMed  CAS  Google Scholar 

  120. Lablanche JM, Grollier G, Lusson JR, Bassand JP, Drobinski G, Bertrand B, et al. 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 1997; 95: 83–89.

    Article  PubMed  Google Scholar 

  121. von der Leyen HE, Gibbons GH, Morishita R, Lewis NP, Zhang L, Nakajima M, et al. Gene therapy inhibiting neointimal vascular lesion: in vivo transfer of endothelial cell nitric oxide synthase gene. Proc Natl Acad Sci USA 1995; 92: 1137–1141.

    Article  PubMed  Google Scholar 

  122. Janssens S, Flaherty D, Nong Z, Varenne O, van Pelt N, Haustermans C, et al. Human endothelial nitric oxide synthase gene transfer inhibits vascular smooth muscle cell proliferation and neointima formation after balloon injury in rats. Circulation 1998; 97: 1274–1281.

    Article  PubMed  CAS  Google Scholar 

  123. Miyagishima M, Tzeng E, Shears LJ, Kawaharada N, Watkins S, Billiar TR. Perivascular iNOS gene transfer using a novel non-occlusive gene delivery device inhibits intimal hyperplasia. Circulation 1997; 96: 113.

    Google Scholar 

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Authors
  1. Robert T. Eberhardt
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  2. Joseph Loscalzo
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Editors and Affiliations

  1. Boston University Medical Center, Boston, MA, USA

    Joseph Loscalzo MD, PHD  & Joseph A. Vita MD  & 

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Eberhardt, R.T., Loscalzo, J. (2000). Nitric Oxide in Atherosclerosis. In: Loscalzo, J., Vita, J.A. (eds) Nitric Oxide and the Cardiovascular System. Contemporary Cardiology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-002-5_16

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  • DOI: https://doi.org/10.1007/978-1-59259-002-5_16

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-101-1

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