Skip to main content
SpringerLink
Log in

Angiotensin II and Nitric Oxide Interaction

  • Chapter
The Role of Nitric Oxide in Heart Failure

Abstract

Nitric oxide degradation linked to endothelial dysfunction plays a central role in cardiovascular diseases. Superoxide producing enzymes such as NADPH oxidase and xanthine oxidase are responsible for NO degradation as they generate a variety of reactive oxygen species (ROS). Moreover, superoxide is rapidly degraded by superoxide dismutase to produce hydrogen peroxide leading to the uncoupling of NO synthase and production of increased amount of superoxide.

Angiotensin II is an important stimulus of NADPH oxidase. Through its AT 1 receptor, Ang II stimulates the long-term increase of several membrane component of NADPH oxidase such as P22 phox or nox-1 and causes an increased activity of NADPH oxidase with inactivation of NO leading to impaired endothelium-dependent vasorelaxation, vascular smooth muscle cell hypertrophy, proliferation and migration, extracellular matrix formation, thrombosis, cellular infiltration and inflammatory reaction. Several preclinical and clinical studies have now confirmed the involvement of the AT 1 receptor in endothelial dysfunction. It is proposed that the AT 2 receptor counterbalances the deleterious effect of the Ang II-induced AT 1 receptor stimulation through bradykinin and NOS stimulation. This mechanism could be especially relevant in pathological cases when the NADPH oxidase activity is blocked with an AT 1 receptor antagonist.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
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

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Hilgers KF, Veelken R, Muller DN, Kohler H, Hartner A, Botkin SR, Stumpf C, Schmieder RE, Gomez RA. Renin uptake by the endothelium mediates vascular angiotensin formation. Hypertension 2001;38:243–248.

    CAS  PubMed  Google Scholar 

  2. Rubanyi GM, Vanhoutte PM. Superoxide anions and hyperoxia inactivate endothelium-derived relaxing factor. Am J Physiol 1986;250:H822–H827.

    CAS  PubMed  Google Scholar 

  3. Taddei S, Virdis A, Mattei P, Arzilli F, Salvetti A. Endothelium-dependent forearm vasodilation is reduced in normotensive subjects with familial history of hypertension. J Card Vasc Pharmacol 1999;20(Suppl 12):S193–S195.

    Google Scholar 

  4. Gaeta G, De Michele M, Cuomo S, Guarini P, Foglia MC, Bond MG, Trevisan M. Arterial abnormalities in the off-spring of patients with premature myocardial infarction. N Engl J Med 2000;343:840–846.

    Article  CAS  PubMed  Google Scholar 

  5. McIntyre M, Bohr DF, Dominiczak AF. Endothelial function in hypertension: The role of superoxide anion. Hypertension 1999;34:539–545.

    CAS  PubMed  Google Scholar 

  6. Griendling KK, Sorescu D, Ushio-Fukai M. NAD(P)H Oxidase: Role in cardiovascular biology and disease. Circ Res 2000;86:494–501.

    CAS  PubMed  Google Scholar 

  7. Cai H, Harrison DG. Endothelial dysfunction in cardiovascular diseases: The role of oxidant stress. Circ Res 2000;87:840–844.

    CAS  PubMed  Google Scholar 

  8. Ruiz-Ortega M, Lorenzo O, Rupérez M, Esteban V, Suzuki Y, Mazzano S, Plaza JJ, Egido J. Role of the renin-angiotensin system in vascular diseases. Expanding the field. Hypertension 2001;38:1382–1387.

    CAS  PubMed  Google Scholar 

  9. Griendling KK, Ushio-Fukai M. Reactive oxygen species as mediators of angiotensin II signaling. Regul Pept 2000;91:21–27.

    Article  CAS  PubMed  Google Scholar 

  10. Dzau VJ. Tissue angiotensin and pathobiology of vascular disease. A unifying hypothesis. Hypertension 2001;37:1047–1052.

    CAS  PubMed  Google Scholar 

  11. John S, Schmieder RE. Impaired endothelial function in arterial hypertension and hypercholesterolemia: Potential mechanisms and differences. J Hypertens 2000;18:363–374.

    Article  CAS  PubMed  Google Scholar 

  12. Bredt DS, Hwang PM, Glatt CE, Lowenstein C, Redd RR, Snyder SH. Cloned and expressed nitric oxide synthase structurally resembles cytochrome P-450 reductase. Nature 1991;351:714–718.

    Article  CAS  PubMed  Google Scholar 

  13. Drexler H, Kastner S, Strobel A, Studer R, Brodde OE, Hasenfuss G. Expression, activity and functional significance of inducible nitric oxide synthase in the failing human heart. J Am Coll Cardiol 1998;32:955–963.

    Article  CAS  PubMed  Google Scholar 

  14. Feng Q, Lu X, Jones DL, Shen J, Arnold JMO. Increased inducible nitric oxide synthase expression contributes to myocardial dysfunction and higher mortality after myocardial infarction in mice. Circulation 2001;104:700–704.

    CAS  PubMed  Google Scholar 

  15. Chyu KY, Dimayuga P, Zhu J, Nilsson J, Kaul S, Shah PK, Cercek B. Decreased neointimal thickening after arterial wall injury in inducible nitric oxide synthase knockout mice. Circ Res 1999;85:1192–1198.

    CAS  PubMed  Google Scholar 

  16. Sausbier M, Schubert R, Voigt V, Hirneiss C, Pfeifer A, Korth M, Kleppisch T, Ruth P, Hofmann F. Mechanism of NO/cGMP-dependent vasorelaxation. Circ Res 2000;87:825–830.

    CAS  PubMed  Google Scholar 

  17. Adachi T, Matsui R, Weisbrod RM, Najibi S, Cohen RA. Reduced sarco/endoplasmic reticulum Ca2+ uptake activity can account for the reduced response to NO, but not sodium nitroprusside, in hypercholesterolemic rabbit aorta. Circulation 2001;104:1040–1045.

    CAS  PubMed  Google Scholar 

  18. Wollert KC, Fiedler B, Gambaryan S, Smolenski A, Heineke J, Butt E, Trautwein C, Lohmann SM, Drexler H. Gene transfer of CGMP-dependent protein kinase I enhances the antihypertrophic effects of nitric oxide in cardiomyocytes. Hypertension 2002;39:87–92.

    Article  CAS  PubMed  Google Scholar 

  19. Kinlay S, Creager MA, Fukumoto M, Hikita H, Fang JC, Selwyn AP, Ganz P. Endothelium-derived nitric oxide regulates arterial elasticity in human arteries in vivo. Hypertension 2001;38:1049–1053.

    CAS  PubMed  Google Scholar 

  20. Wilkinson IB, Qasem A, McEniery CM, Webb DJ, Avolio AP, Cockcroft JR. Nitric oxide regulates local arterial distensibility in vivo. Circulation 2002;105:213–217.

    Article  CAS  PubMed  Google Scholar 

  21. MacCarthy PA, Grieve DJ, Li JM, Dunster C, Kelly FJ, Shah AM. Impaired endothelial regulation of ventricular relaxation in cardiac hypertrophy: Role of reactive oxygen species and NADPH oxidase. Circulation 2001;104:2967–2974.

    CAS  PubMed  Google Scholar 

  22. Zalba G, Beaumont FJ, San Jose G, Fortuno A, Fortuno MA, Diez J. Is the balance between nitric oxide and superoxide altered in spontaneously hypertensive rats with endothelial dysfunction? Nephrol Dial Transplant 2001;16(Suppl 1):2–5.

    CAS  PubMed  Google Scholar 

  23. Wiemer G, Itter G, Malinski T, Linz W. Decreased nitric oxide availability in normotensive and hypertensive rats with failing hearts after myocardial infarction. Hypertension 2001;38:1367–1371.

    CAS  PubMed  Google Scholar 

  24. Sventek P, Li JS, Grove K, Deschepper CE, Schiffrin EL. Vascular structure and expression of endothelin-1 gene in L-NAME treated spontaneously hypertensive rats. Hypertension 1996;27:49–55.

    CAS  PubMed  Google Scholar 

  25. Takemoto M, Egashira K, Tomita H, Usui M, Okamoto H, Kitabatake A, Shimokawa H, Sueishi K, Takeshita A. Chronic angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor blockade: Effects on cardiovascular remodeling in rats induced by the long-term blockade of nitric oxide synthesis. Hypertension 1997;30:1621–1627.

    CAS  PubMed  Google Scholar 

  26. Tomita H, Egashira K, Ohara Y, Takemoto M, Koyanagi M, Katoh M, Yamamoto H, Tamaki K, Shimokawa H, Takeshita A. Early induction of transforming growth factor-β via angiotensin II type 1 receptors contributes to cardiac fibrosis induced by long-term blockade of nitric oxide synthesis in rats. Hypertension 1988;32:273–279.

    Google Scholar 

  27. Kashiwagi M, Shinozaki M, Hirakata H, Tamaki K, Hirano T, Tokumoto M, Goto H, Okuda S, Fujishima M. Locally activated renin-angiotensin system associated with TGF-beta 1 as a major factor for renal injury induced by chronic inhibition of nitric oxide synthase in rats. J Am Soc Nephrol 2000;11:616–624.

    CAS  PubMed  Google Scholar 

  28. Koyanagi M, Egashira K, Kitamoto S, Ni W, Shomokawa H, Takeya M, Yoshimura T, Takeshita A. Role of monocyte chemoattractant protein-1 in cardiovascular remodeling induced by chronic blockade of nitric oxide synthesis. Circulation 2000;102:2243–2248.

    CAS  PubMed  Google Scholar 

  29. Usui M, Egashira K, Tomita H, Koyanagi M, Katoh M, Shimokawa H, Takeya M, Yoshimura T, Matsushima K, Takeshita A. Important role of local angiotensin II activity mediated via type 1 receptor in pathogenesis of cardiovascular inflammatory changes induced by chronic blockade of nitric oxide synthesis in rats. Circulation 2000;101:305–310.

    CAS  PubMed  Google Scholar 

  30. Szöcs K, Lassègue B, Sorescu D, Hilenski LL, Valppu L, Couse TL, Wilcox JN, Quinn MT, Lambeth JD, Griendling KK. Upregulation of NOx based NAD(P)H oxidases in restenosis after carotid injury. Arterioscler Thromb Vasc Biol 2002;22:21.

    PubMed  Google Scholar 

  31. Poderoso JJ, Carreras MC, Lisdero C, Riobo N, Schopfer F, Boveris. A nitric oxide inhibits electron transfer and increases superoxide radical production in rat heart mitochondria and submitochondrial particles. Arch Biochem Biophys 1996;328:85–92.

    Article  CAS  PubMed  Google Scholar 

  32. Suzuki H, Swei A, Zweifach BW, Schmid-Schonbein GW. In vivo evidence for microvascular oxidative stress in spontaneously hypertensive rats. Hydroethidine microfluorography. Hypertension 1995;25:1083–1089.

    CAS  PubMed  Google Scholar 

  33. Wu L, deChamplain J. Effects of superoxide on signaling pathways in smooth muscle cells from rats. Hypertension 1999;34:1247–1253.

    CAS  PubMed  Google Scholar 

  34. Laursen JB, Rajagopalan S, Galis Z, Tarpey M, Freeman BA, Harrison DG. Role of superoxide in angiotensin II induced but not catecholamine-induced hypertension. Circulation 1997;95:588–593.

    CAS  PubMed  Google Scholar 

  35. Griendling KK, Minieri CA, Ollerenshaw JD, Alexander RW. Angiotensin II stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells. Circ Res 1994;74:1141–1148.

    CAS  PubMed  Google Scholar 

  36. Baas AS, Berk BC. Differential activation of mitogenactivated protein kinases by H 2 O 2 and O 2 -in vascular smooth muscle cells. Circ Res 1995;77:29–36.

    CAS  PubMed  Google Scholar 

  37. Touyz RM, Schiffrin EL. Ang II-stimulated superoxide production is mediated via phospholipase D in human vascular smooth muscle cells. Hypertension 1999;34:976–982.

    CAS  PubMed  Google Scholar 

  38. Beckman JA, Goldfine AB, Gordon MB, Garrett LA, Creager MA. Inhibition of protein kinase Cβ prevents impaired endothelium-dependent vasodilation caused by hyperglycemia in humans. Circ Res 2002;90:107–111.

    Article  CAS  PubMed  Google Scholar 

  39. Zalba G, Jose GS, Moreno MU, Fortuno MA, Fortuno A, Beaumont FJ, Diez J. Oxidative stress in arterial hypertension: Role of NAD(P)H oxidase. Hypertension 2001;38:1395–1399.

    CAS  PubMed  Google Scholar 

  40. Eguchi S, Numaguchi K, Iwasaki H, Matsumoto T, Yamakawa T, Utsunomya H, Motley ED, Kawakatsu H, Owada KM, Hirata Y, Marumo F, Inagami T. Calcium-dependent epidermal growth factor receptor transactivation mediates the angiotensin II-induced mitogen-activated protein kinase activation in vascular smooth muscle cells. J Biol Chem 1998;273:8890–8896.

    Article  CAS  PubMed  Google Scholar 

  41. Murasawa S, Mori Y, Nozawa Y, Gotoh N, Shibuya M, Masaki H, Maruyama K, Tsutsumi Y, Moriguchi Y, Shibazaki Y, Tanaka Y, Iwasaka T, Inada M, Matsubara H. Angiotensin II type 1 receptor-induced extracellular signal-regulated protein kinase activation is mediated by Ca2+/calmodulin-dependent transactivation of epidermal growth factor receptor. Circ Res 1998;82:1338–1348.

    CAS  PubMed  Google Scholar 

  42. Ushio-Fukai M, Griendling KK, Becker PL, Hilenski L, Halleran S, Alexander RW. Epidermal growth factor receptor transactivation by angiotensin II requires reactive oxygen species in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 2001;21:489–495.

    CAS  PubMed  Google Scholar 

  43. Heeneman S, Haendeler J, Saito Y, Ishida M, Berk BC. Angiotensin II induces transactivation of two different populations of the platelet-derived growth factor beta receptor. Key role for the p66 adaptor protein Shc. J Biol Chem 2000;275:15926–15932.

    Article  CAS  PubMed  Google Scholar 

  44. Du J, Sperling LS, Marrero MB, Phillips L, Delafontaine P. G-protein and tyrosine kinase receptor cross-talk in rat aortic smooth muscle cells: Thrombin-and angiotensin II-induced tyrosine phosphorylation of insulin receptor substrate-1 and insulin-like growth factor 1 receptor. Biochem Biophys Res Commun 1996;218:934–939.

    Article  CAS  PubMed  Google Scholar 

  45. Rajagopalan S, Kurz S, Münzel T, Tarpey M, Freeman BA, Griendling KK, Harrison DG. Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. J Clin Invest 1996;97:1916–1923.

    CAS  PubMed  Google Scholar 

  46. Fukui T, Ishizaka N, Rajagopalan S, Laursen JB, Capers Q, Taylor WR, Harrison DG, De Leon H, Wilcox JN, Griendling KK. p22phox mRNA expression and nadph oxidase activity are increased in aortas from hypertensive rats. Circ Res 1997;80:45–51.

    CAS  PubMed  Google Scholar 

  47. Ushio-Fukai M, Zafari AM, Fukui T, Ishizaka N, Griendling KK. p22phox is a critical component of the superoxide-generating NADH/NADPH oxidase system and regulates angiotensin iiinduced hypertrophy in vascular smooth muscle cells. J Biol Chem 1996;271:23317–23321.

    CAS  PubMed  Google Scholar 

  48. Ushio-Fukai M, Alexander RW, Akers M, Griendling KK. p38 Mitogen-activated protein kinase is a critical component of the redox-sensitive signaling pathways activated by angiotensin II. Role in vascular smooth muscle cell hypertrophy. J Biol Chem 1998;273:15022–15029.

    CAS  PubMed  Google Scholar 

  49. Finta KM, Fischer MJ, Lee L, Gordon D, Pitt B, Webb RC. Ramipril prevents impaired endothelium-dependent relaxation in arteries from rabbits fed an atherogenic diet. Atherosclerosis 1993;100:149–156.

    Article  CAS  PubMed  Google Scholar 

  50. Munzel T, Keaney JF. Are ACE inhibitors a “magic bullet” against oxidative stress? Circulation 2001;104:1571–1574.

    CAS  PubMed  Google Scholar 

  51. Hornig B, Landmesser U, Kohler C, Ahlersmann D, Spiekermann S, Christoph A, Tatge H, Drexler H. Comparative effect of ACE inhibition and angiotensin II type 1 receptor antagonism on bioavailability of nitric oxide in patients with coronary artery disease. Role of superoxide dismutase. Circulation 2001;103:799–805.

    CAS  PubMed  Google Scholar 

  52. Sadoshima J, Xu Y, Slayter HS, Izumo S. Autocrine release of angiotensin II mediates stretch-induced hypertrophy of cardiac myocytes in vitro. Cell 1993;75:977–984.

    Article  CAS  PubMed  Google Scholar 

  53. Marklund SL. Expression of extracellular superoxide dismutase by human cell lines. Biochem J 1990;266:213–219.

    CAS  PubMed  Google Scholar 

  54. Pueyo ME, Arnal JF, Rami J, Michel JB. Angiotensin II stimulates the production of NO and peroxynitrite in endothelial cells. Am J Physiol Cell Physiol 1998;274:C214–C220.

    CAS  Google Scholar 

  55. Zafari AM, Ushio-Fukai M, Akers M, Yin Q, Shah A, Harrison DG, Taylor WR, Griendling KK. Role of NADH/NADPH oxidase-derived H 2 O 2 in angiotensin II-induced vascular hypertrophy. Hypertension 1998;32:488–495.

    CAS  PubMed  Google Scholar 

  56. Matoba T, Shimokawa H, Kubota H, Morikawa K, Jujiki T, Kunihiro I, Mukai Y, Hirakawa Y, Takeshita A. Hydrogen peroxide is an endothelium-derived hyperpolarizing factor in human mesenteric arteries. Biochem Biophys Res Commun 2002;25:909–913.

    Google Scholar 

  57. Vanhoutte P. Endothelium-derived free radicals: For worse and for better. J Clin Invest 2001;107:23–25.

    CAS  PubMed  Google Scholar 

  58. Matrougui K, Loufrani L, Heymes C, Levy BI, Henrion D. Activation of AT 2 receptors by endogenous angiotensin II is involved in flow-induced dilation in rat resistance arteries. Hypertension 1999;34:659–665.

    CAS  PubMed  Google Scholar 

  59. Yamazaki T, Komuro I, Kudoh S, Zou Y, Shiojima I, Mizuno T, Takano H, Hiroi Y, Ueki K, Tobe K, Kadowaki T, Nagai R, Yazaki Y. Angiotensin II partly mediates mechanical stress-induced cardiac hypertrophy. Circ Res 1995;77:258–265.

    CAS  PubMed  Google Scholar 

  60. Takagishi T, Murahashi N, Azagami S, Morimatsu M, Sasaguri Y. Effect of angiotensin II and thromboxane A2 on the production of matrix metalloproteinase Hy human aortic smooth muscle cells. Biochem Mol Biol Int 1995;35:265–273.

    CAS  PubMed  Google Scholar 

  61. Vaughan DE, Lazos SA, Tong K. Angiotensin II regulates the expression of plasminogen activator inhibitor in cultured endothelial cells. A potential link between the renin-angiotensin and thrombosis. J Clin Invest 1995;95:995–1001.

    CAS  PubMed  Google Scholar 

  62. Sironi L, Calvio AM, Arnaboldi L, Corsini A, Parolari A, de Gasparo M, Tremoli E, Mussoni L. Effect of valsartan on angiotensin II-induced plasminogen activator inhibitor-1 biosynthesis in arterial smooth muscle cells. Hypertension 2001;37:961–966.

    CAS  PubMed  Google Scholar 

  63. Oubiña MP, de las Heras N, Vázquez-Pérez S, Cediel E, Sanz-Rosa D, Ruilope LM, Cachofeiro V, Lahera V. Valsartan improves fibrinolytic balance in atheroslerotic rabbits. J Hypertens 2000;20:303–310.

    Google Scholar 

  64. Tummala PE, Chen XL, Sundell CL, Laursen JB, Hammes CP, Alexander RW, Harrison DG, Medford RIM. Angiotensin II induces vascular cell adhesion molecule-1 expression in rat vasculature: A potential link between the renin-angiotensin system and atherosclerosis. Circulation 1999;100:1223–1229.

    CAS  PubMed  Google Scholar 

  65. Mervaala EM, Muller DN, Park JK, Schmidt F, Lohn M, Breu V, Dragun D, Ganten D, Haller H, Luft FC. Monocyte infiltration and adhesion molecules in a rat model of high human renin hypertension. Hypertension 1999;33:389–395.

    CAS  PubMed  Google Scholar 

  66. Rakugi H, Kim DK, Krieger JE, Wang DS, Dzau VJ, Pratt RE. Induction of angiotensin converting enzyme in the neointima after vascular injury. Possible role in restenosis. J Clin Invest 1994;93:339–346.

    CAS  PubMed  Google Scholar 

  67. Diet F, Pratt RE, Berry GJ, Momose N, Gibbons GH, Dzau VJ. Increased accumulation of tissue ACE in human atherosclerotic coronary disease. Circulation 1996;94:2756–2767.

    CAS  PubMed  Google Scholar 

  68. Ichiki T, Usui M, Kato M, Funakoshi Y, Ito K, Egashira K, Takeshita A. Downregulation of angiotensin II type 1 receptor gene transcription by nitric oxide. Hypertension 1998;31:342–348.

    CAS  PubMed  Google Scholar 

  69. Usui M, Ichiki T, Katoh M, Egashira K, Takeshita A. Regulation of angiotensin II receptor expression by nitric oxide in rat adrenal gland. Hypertension 1998;32:527–533.

    CAS  PubMed  Google Scholar 

  70. Warnholtz A, Nickenig G, Schulz E, Macharzina R, Brasen JH, Skatchkov M, Heitzer T, Stasch JP, Griendling KK, Harrison DG, Bohm M, Meinertz T, Munzel T. Increased NADH-oxidase-mediated superoxide production in the early stages of atherosclerosis: Evidence for involvement of the renin-angiotensin system. Circulation 1999;99:2027–2033.

    CAS  PubMed  Google Scholar 

  71. Lemay J, Hou Y, deBlois D. Evidence that nitric oxide regulates AT 1 receptor agonist and antagonist efficacy in rat injured carotid artery. J Cardiovasc Pharmacol 2000;35:693–699.

    Article  CAS  PubMed  Google Scholar 

  72. Mancini GBJ, Henry GC, Macaya C, O’Neill BJ, Pucillo AL, Carere RG, Wargovich TJ, Mudra H, Lüscher TF, Klibaner MI, Haber HE, Uprichard ACG, Pepine CJ, Pitt B. Angiotensin-converting enzyme inhibition with quinapril improves endothelial vasomotor dysfunction in patients with coronary artery disease. The TREND (Trial on Reversing ENdothelial Dysfunction) study. Circulation 1996;94:258–265.

    CAS  PubMed  Google Scholar 

  73. Svensson P, de Faire U, Sleight P, Yusuf S, Ostergren J. Comparative effects of ramipril on ambulatory and office blood pressures: A HOPE substudy. Hypertension 2001;38:E28–E32.

    CAS  PubMed  Google Scholar 

  74. Schiffrin EL, Park JB, Intengan HD, Touyz RM. Correction of arterial structure and endothelial dysfunction in human essential hypertension by the angiotensin receptor antagonist losartan. Circulation 2000;101:1653–1659.

    CAS  PubMed  Google Scholar 

  75. Schiffrin EL, Park JB, Pu Q. Effect of crossing over hypertensive patients from a beta-blocker to an angiotensin receptor antagonist on resistance artery structure and on endothelial function. J Hypertens 2002;20:71–78.

    CAS  PubMed  Google Scholar 

  76. Boulanger CM, Caputo L, Levy BI. Endothelial AT 1 -mediated release of nitric oxide decreases angiotensin II contractions in rat carotid artery. Hypertension 1995;26:752–757.

    CAS  PubMed  Google Scholar 

  77. Dobrian AD, Schriver SD, Prewitt RL. Role of angiotensin II and free radicals in blood pressure regulation in a rat model of renal hypertension. Hypertension 2001;38:361–366.

    CAS  PubMed  Google Scholar 

  78. Brosnan MJ, Hamilton CA, Graham D, Lygate CA, Jardine E, Dominiczak AF. Irbesartan lowers superoxide levels and increases nitric oxide bioavailability in blood vessels from spontaneously hypertensive stroke-prone rats. J Hypertens 2002;20:281–286.

    Article  CAS  PubMed  Google Scholar 

  79. Khaper N, Singal PK. Modulation of oxidative stress by a selective inhibition of angiotensin II type 1 receptors in MI rats. J Am Coll Cardiol 2001;37:1461–1466.

    Article  CAS  PubMed  Google Scholar 

  80. Khan BV, Navalkar S, Khan QA, Rahman ST, Parthasarathy S. Irbesartan, an angiotensin type 1 receptor inhibitor, regulates the vascular oxidative state in patients with coronary artery disease. J Am Coll Cardiol 2001;38:1662–1667.

    CAS  PubMed  Google Scholar 

  81. Bunkenburg B, Schnell C, Baum HP, Cumin F, Wood JM. Prolonged angiotensin II antagonism in spontaneously hypertensive rats. Hemodynamic and biochemical consequences. Hypertension 1991;18:278–288.

    CAS  PubMed  Google Scholar 

  82. Christen Y, Waeber B, Nussberger J, Borland RM, Lee RJ, Maggon K, Shum L, Timmermans PB, Brunner HR. Oral administration of Dup 753, a specific angiotensin II receptor antagonist in normal volunteers. Inhibition of pressore response to exogenous angiotensin I and II. Circulation 1991;83:1333–1342.

    CAS  PubMed  Google Scholar 

  83. Mazzolai L, Maillard M, Rossat J, Nussberger J, Brunner HR, Burnier M. Angiotensin II receptor blockade in normotensive subjects: A direct comparison of three AT 1 receptor antagonists. Hypertension 1999;33:850–855.

    PubMed  Google Scholar 

  84. Rogg H, de Gasparo M, Graedel E, Stulz P, Burkart F, Eberhard M, Erne P. Angiotensin II-receptor subtypes in human atria and evidence for alterations in patients with cardiac dysfunction. Eur Heart J 1996;17:1112–1120.

    CAS  PubMed  Google Scholar 

  85. Tsutsumi Y, Matsubara H, Ohkubo N, Mori Y, Nozawa Y, Murasawa S, Kijima K Maruyama K, Masaki H, Moriguchi Y, Shibasaki Y, Kamiha H, Inada M, Iwasaka T. Angiotensin II type 2 receptor is upregulated in human heart with interstitial fibrosis and cardiac fibroblasts are the major cell type for its expression. Circ Res 1998;83:1035–1046.

    CAS  PubMed  Google Scholar 

  86. Hutchinson HG, Hein L, Fujinaga M, Pratt RE. Modulation of vascular development and injury by angiotensin II. Cardiovasc Res 1999;41:689–700.

    Article  CAS  PubMed  Google Scholar 

  87. Ozono R, Wang ZQ, Moore AF, Inagami T, Siragy HM, Carey RM. Expression of the subtype 2 angiotensin (AT 2 ) receptor protein in rat kidney. Hypertension 1997;30:1238–1246.

    CAS  PubMed  Google Scholar 

  88. de Gasparo M, Siragy HM. The AT 2 receptor: Fact, fancy and fantasy. Regul Pept 1999;81:11–24.

    PubMed  Google Scholar 

  89. Masaki H, Kurihara T, Yamaki A, Inomata N, Nozawa Y, Mori Y, Murasawa S, Kizima K, Maruyama K, Horiuchi M, Dzau VJ, Takahashi H, Iwasaka T, Inada M, Matsubara H. Cardiac-specific overexpression of angiotensin II AT 2 receptor causes attenuated response to AT 1 receptor-mediated pressor and chronotropic effects. J Clin Invest 1998;101:527–535.

    CAS  PubMed  Google Scholar 

  90. Carey RM, Wang ZQ, Siragy HM. Update: Role of the angiotensin type-2 (AT(2)) receptor in blood pressure regulation. Curr Hypertens Rep 2000;2:198–201.

    CAS  PubMed  Google Scholar 

  91. Horiuchi M, Akishita M, Dzau VJ. Recent progress in angiotensin II type 2 receptor research in the cardiovascular system. Hypertension 1999;33:613–621.

    CAS  PubMed  Google Scholar 

  92. Siragy HM, Carey RM. The subtype-2 (AT 2 ) angiotensin receptor regulates renal cyclic guanosine 3′,5′-monophosphate and AT 1 receptor-mediated prostaglandin E2 production in conscious rats. J Clin Invest 1996;97:1978–1982.

    CAS  PubMed  Google Scholar 

  93. Siragy HM, Jaffa AA, Margolius HS, Carey RM. Renin-angiotensin system modulates renal bradykinin production. Am J Physiol 1996;271:R1090–R1095.

    CAS  PubMed  Google Scholar 

  94. Siragy HM, Carey RM. The subtype 2 (AT 2 ) angiotensin receptor mediates renal production of nitric oxide in conscious rats. J Clin Invest 1997;100:264–269.

    CAS  PubMed  Google Scholar 

  95. Tsutsumi Y, Matsubara H, Masaki H, Kurihara H, Murasawa S, Takai S, Miyazaki M, Nozawa Y, Ozono R, Nakagawa K, Miwa T, Kawada N, Mori Y, Shibasaki Y, Tanaka Y, Fujiama S, Koyama Y, Fujiyama A, Takahashi H, Iwasaka T. Angiotensin II type 2 receptor overexpression activates the vascular kinin system and causes vasodilation. J Clin Invest 1999;104:925–935.

    CAS  PubMed  Google Scholar 

  96. Yang XP, Liu YH, Mehta D, Cavasin MA, Shesely E, Xu J, Liu F, Carretero OA. Diminished cardioprotective response to inhibition of angiotensin-converting enzyme and angiotensin II type 1 receptor in B(2) kinin receptor gene knockout mice. Circ Res 2001;88:1072–1079.

    CAS  PubMed  Google Scholar 

  97. Guan H, Cachofeiro V, Pucci ML, Kaminski PM, Wolin MS, Nasjletti A. Nitric oxide and the depressor response to angiotensin blockade in hypertension. Hypertension 1996;27:19–24.

    CAS  PubMed  Google Scholar 

  98. Liu YH, Yang XP, Sharov VG, Nass O, Sabbah HN, Peterson E, Carretero OA. Effects of angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor antagonists in rate with heart failure. Role of kinins and angiotensin II type 2 receptors. J Clin Invest 1997;99:1926–1935.

    CAS  PubMed  Google Scholar 

  99. Gohlke P, Pees C, Unger T. AT 2 receptor stimulation increases aortic cyclic GMP in SHRSP by a kinin-dependent mechanism. Hypertension 1998;81:349–355.

    Google Scholar 

  100. Wu L, Iwai M, Nakagami H, Chen R, Suzuki J, Akishita M, de Gasparo M, Horiuchi M. Effect of angiotensin II Type 1 receptor blockade on cardiac remodeling in angiotensin ii type 2 receptor null mice. Arterioscler Thromb Vase Biol 2002;22:49–54.

    Google Scholar 

  101. Sohn HY, Raff U, Hoffmann A, Gloe T, Heermeier K, Galle J, Pohl U. Differential role of angiotensin II receptor subtypes on endothelial superoxide formation. Br J Pharmacol 2000;131:667–672.

    Article  CAS  PubMed  Google Scholar 

  102. Nouet S, Nahmias C. Signal transduction from the angiotensin II AT 2 receptor. Trends Endocrinol Metab 2000;11:1–6.

    CAS  PubMed  Google Scholar 

  103. Sartore S, Chiavegato A, Faggin E, Franch R, Puato M, Ausoni S, Pauletto P. Contribution of adventitial fibroblasts to neointima formation and vascular remodeling: From innocent bystander to active participant. Circ Res 2001;89:1111–1121.

    CAS  PubMed  Google Scholar 

  104. Scheidegger KJ, Wood JM. Local application of angiotensin II to the rat carotid artery induces adventitial thickening. J Vasc Res 1997;34:436–446.

    CAS  PubMed  Google Scholar 

  105. Peters S, Gotting B, Trummel M, Rust H, Brattstrom A. Valsartan for prevention of restenosis after stenting of type B2/C lesions: The VAL-PREST trial. J Invasive Cardiol 2001;13:93–97.

    CAS  PubMed  Google Scholar 

  106. Siragy HM, de Gasparo M, Carey RM. Angiotensin type 2 receptor mediates valsartan-induced hypotension in conscious rats. Hypertension 2000;35:1074–1077.

    CAS  PubMed  Google Scholar 

  107. Siragy HM, de Gasparo M, El Kersh M, Carey RM. Angiotensin-converting enzyme inhibition potentiates angiotensin II type 1 receptor effects on renal bradykinin and cGMP. Hypertension 2001;38:183–186.

    CAS  PubMed  Google Scholar 

  108. Barber MN, Sampey DB, Widdop RE. AT 2 receptor stimulation enhances antihypertensive effects of AT1 receptor antagonist in hypertensive rate. Hypertension 1999;34:1117–1122.

    Google Scholar 

  109. Carey RM, Howell NL, Jin XH, Siragy HM. Angiotensin type 2 receptor-mediated hypotension in angiotensin type-1 receptor-blocked rats. Hypertension 2001;38:1272–1277.

    CAS  PubMed  Google Scholar 

  110. Schuijt MP, de Vries R, Saxena PR, Danser AH. No vasoactive role of the angiotensin II type 2 receptor in normotensive Wistar rats. J Hypertens 1999;17:1879–1884.

    CAS  PubMed  Google Scholar 

  111. Schuijt MP, Basdew M, van Veghel R, de Vries R, Saxena PR, Schoemaker RG, Danser AH. AT(2) receptor-mediated vasodilation in the heart: Effect of myocardial infarction. Am J Physiol Heart Circ Physiol 2001;281:H2590–H2596.

    CAS  PubMed  Google Scholar 

  112. Katoh M, Egashira K, Usui M, Shimokawa H, Rakugi H, Takeshita A. Cardiac angiotensin II receptors are upregulated by long-term inhibition of nitric oxide synthesis in rats. Circ. Res 1998;83:743–751.

    CAS  PubMed  Google Scholar 

  113. Uhlenius N, Vuolteenabo O, Tikkanen I. Renin-angiotensin blockade improves rebal cGMP production via non-AT2-receptor mediated mechanisms in hypertension-induced by chronic NOS inhibition in rat. JRAAS 2001;2:233–239.

    CAS  PubMed  Google Scholar 

  114. Nakamura Y, Ono H, Zhou X, Frohlich ED. Angiotensin type 1 receptor antagonism and ACE inhibition produce similar renoprotection in N-nitro-L-arginine methyl ester/spontaneously hypertensive rats. Hypertension 2001;37:1262–1267.

    CAS  PubMed  Google Scholar 

  115. van Ampting JM, Hijmering ML, Beutler JJ, van Etten RE, Koomans HA, Rabelink TJ, Stroes ES. Vascular effects of ace inhibition independent of the renin-angiotensin system in hypertensive renovascular disease: A randomized, double-blind, crossover trial. Hypertension 2001;37:40–45.

    PubMed  Google Scholar 

  116. Gallinat S, Busche S, Schütze S, Krönke M, Unger T. AT 2 receptor stimulation induces generation of ceramides in PC12W cells. FEBS Lett 1999;443:75–79.

    Article  CAS  PubMed  Google Scholar 

  117. Lehtonen JY, Horiuchi M, Daviet L, Akishita M, Dzau VJ. Activation of the de novo biosynthesis of sphyngolipids mediates angiotensin II type 2 receptor-induced apoptosis. JBiol Chem 1999;274:16901–16906.

    CAS  Google Scholar 

  118. Zhang DX, Zou AP, Li PL. Ceramide reduces endothelium-dependent-vasodilation by increasing superoxide production in small bovine coronary arteries. Circ Res 2001;88:824.

    CAS  PubMed  Google Scholar 

  119. Ruiz-Ortega M, Lorenzo O, Rupérez M, König S, Wittig B, Egido J. Angiotensin II activates nuclear transcription factor κB trough AT 1 and AT 2 in vascular smooth muscle cells. Molecular mechanisms. Circ Res 2000;86:1266–1272.

    CAS  PubMed  Google Scholar 

  120. Cao Z, Kelly DJ, Cox A, Casley D, Forbes JM, Martinello P, Dean R, Gilbert RE, Cooper, ME. Angiotensin type 2 receptor is expressed in the adult rat kidney and promotes cellular proliferation and apoptosis. Kidney Int 2000;58:2437–2451.

    Article  CAS  PubMed  Google Scholar 

  121. de Gasparo M, Catt KJ, Inagami T, Wright JW, Unger T. International Union of Pharmacology. XXIII. The Angiotensin II receptors. Pharmacol Rev 2001;52:415–472.

    Google Scholar 

  122. Heitsch H, Brovkovych S, Malinski T, Wiemer G. Angiotensin-(1–7)-stimulated nitric oxide and superoxide release from endothelial cells. Hypertension 2001;37:72.

    CAS  PubMed  Google Scholar 

  123. Ren YL, Garvin JL, Carretero OA. Vasodilator action of angiotensin-(1–7) on isolated rabbit afferent arterioles. Hypertension 2002;39:799–802.

    CAS  PubMed  Google Scholar 

  124. Kramar EA, Harding JW, Wright JW. Angiotensin II-and IV-induced changes in cerebral blood flow. Roles of AT 1 AT 2 , and AT 4 receptor subtypes. Regul Pept 1997;68:131–138.

    CAS  PubMed  Google Scholar 

  125. Patel M, Martens JR, Li YD, Gelband CH, Raizada MK, Block ER. Angiotensin IV receptor-mediated activation of lung endothelial NOS is associated with vasorelaxation. Am J Physiol 1998;275:L1061–L1068.

    CAS  PubMed  Google Scholar 

  126. Farquharson CAJ, Struthers AD. Spironolactone increases nitric oxide bioactivity, improves endothelial vasodilator dysfunction, and suppresses vascular angiotensin I/angiotensin II conversion in patients with chronic heart failure. Circulation 2000;101:594–597.

    CAS  PubMed  Google Scholar 

  127. Raij L. Hypertension and cardiovascular risk factors. Role of the angiotensin II-nitric oxide interaction. Hypertension 2001;37:767–773.

    CAS  PubMed  Google Scholar 

  128. Vapaatalo H, Mervaala E. Clinically important factors influencing endothelial function. Med Sci Monit 2001;7:1075–1085.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. MG Consulting Co, Rossemaison, Switzerland

    Marc de Gasparo MD

Authors
  1. Marc de Gasparo MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Cardiology Division Department of Medicine, University of Alberta, Edmonton, Alberta, Canada

    Bodh I. Jugdutt

Rights and permissions

Reprints and permissions

Copyright information

© 2004 Kluwer Academic Publishers

About this chapter

Cite this chapter

de Gasparo, M. (2004). Angiotensin II and Nitric Oxide Interaction. In: Jugdutt, B.I. (eds) The Role of Nitric Oxide in Heart Failure. Springer, Boston, MA. https://doi.org/10.1007/1-4020-7960-5_12

Download citation

  • DOI: https://doi.org/10.1007/1-4020-7960-5_12

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4020-7736-4

  • Online ISBN: 978-1-4020-7960-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation