Skip to main content

Angiotensin II Receptor Antagonism in an Ovine Model of Heart Failure Comparison with ACE and Renin Inhibition

  • Chapter
Angiotensin Receptors

Abstract

Over the last three decades, great strides have been made in our understanding of the pathophysiology of congestive heart failure, particularly with regard to the central role of the renin—angiotensin system (RAS), which is activated early in the course of heart failure. These findings are highlighted by recent studies that demonstrate improved survival in patients with heart failure and left ventricular dysfunction treated with angiotensin-converting enzyme (ACE) inhibitors.1–3 However, questions remain about the specificity of these agents for blocking the RAS. Angiotensin II (ANG II), which is central to the activity of this important system, exerts numerous effects on a variety of vascular and nonvascular tissues due to the activation of specific ANG II receptors on the cell surface.4–6 The recent development of specific AT1 receptor antagonists (AT1A) and the ability to analyze receptor numbers allow investigation of the central role of AT1 receptors in modulating the effects of activation of the RAS in heart failure.

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

Access this chapter

eBook
USD 16.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 16.99
Price excludes VAT (USA)
  • Compact, lightweight 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. CONSENSUS Trial Study Group: Effects of enalapril on mortality in severe congestive heart failure. N Engl J Med 316:1429–1435, 1987.

    Article  Google Scholar 

  2. SOLVD Investigators: Effects of enalapril on survival in patients with reduced left ventricular ejection fraction and congestive heart failure. N Engl J Med 325:293–302, 1991.

    Article  Google Scholar 

  3. Pfeffer MA, Braunwald E, Moye LA, et al: Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction: Results of the Survival and Ventricular Enlargement Trial. N Engl J Med 327:669–677, 1992.

    Article  PubMed  CAS  Google Scholar 

  4. Rogg H, Schmid A, de Gaspara M: Identification and characterization of angiotensin II receptor subtypes in rabbit ventricular myocardium. Biochem Biophys Res Commun 173:416–422, 1990.

    Article  PubMed  CAS  Google Scholar 

  5. Tsutsumi K, Saavedra JM: Quantitative autoradiography reveals different angiotensin II receptor subtypes in selected rat brain nuclei. J Neurochem 56:348–351, 1991.

    Article  PubMed  CAS  Google Scholar 

  6. Wong PC, Hart SD, Zaspel AM, et al: Functional studies of nonpeptide angiotensin II receptor subtype-specific ligands: DuP 753 (AII-1) and PD 123177 (AII-2). J Pharmacol Exp Ther 255:584–592, 1990.

    PubMed  CAS  Google Scholar 

  7. Franciosa JA. Cardiology Update: Reviews for Physicians. Churchill-Livingstone, Edinburgh, 1981

    Google Scholar 

  8. Fitzpatrick MA, Nicholls MG, Espiner EA, et al: Neurohumoral changes during onset and offset of ovine heart failure: Role of ANP. Am J Physiol 256:H1052–1059, 1989.

    PubMed  CAS  Google Scholar 

  9. Fitzpatrick MA, Rademaker MT, Frampton CM, et al: Hemodynamic and hormonal effects of renin inhibition in ovine heart failure. Am J Physiol 258:H1625–1631, 1990.

    PubMed  CAS  Google Scholar 

  10. Fitzpatrick MA, Rademaker MT, Frampton CM, et al: Renal effects of ACE inhibition in ovine heart failure: A comparison of intermittent and continuous ACE inhibition. J Car-diovasc Pharmacol 16:629–635, 1990.

    Article  CAS  Google Scholar 

  11. Fitzpatrick MA, Yandle TG, Espiner EA, et al: ANP infusion in the treatment of heart failure and comparison with ACE inhibition. J Cardiovasc Pharmacol 15:536–543, 1990.

    Article  PubMed  CAS  Google Scholar 

  12. Fitzpatrick MA, Rademaker MT, Charles CJ, et al: Angiotensin II receptor antagonism in ovine heart failure: Acute hemodynamic, hormonal and renal effects. Am J Physiol 263:H250–256, 1992.

    PubMed  CAS  Google Scholar 

  13. Fitzpatrick MA, Rademaker MT, Yandle TG, et al: Comparison of the effect on renin inhibition and angiotensin-converting enzyme inhibition in heart failure. J Cardiovasc Pharmacol 19:169–175, 1992.

    Article  PubMed  CAS  Google Scholar 

  14. Riegger AJG, Liebau G: The renin—angiotensin—aldosterone system, antidiuretic hormone and sympathetic nerve activity in an experimental model of congestive heart failure in the dog. Clin Sci 62:465–469, 1982.

    PubMed  CAS  Google Scholar 

  15. Riegger AJG, Liebau G, Holzschuh M, et al: Role of the renin—angiotensin system in the development of congestive heart failure in the dog as assessed by chronic converting enzyme blockade. Am J Cardiol 53:614–618, 1984.

    Article  PubMed  CAS  Google Scholar 

  16. Wilson JR, Douglas P, Hickey WF, et al: Experimental congestive heart failure produced by ventricular pacing in the dog: Cardiac effects. Circulation 75:857–867, 1987.

    Article  PubMed  CAS  Google Scholar 

  17. Howard RJ, Stopps TP, Moe GW, et al: Recovery from heart failure: Structural and functional analysis in a canine model. Can J Physiol Pharmacol 66:1505–1512, 1988.

    Article  PubMed  CAS  Google Scholar 

  18. Tomita M, Spinale FG, Crawford FA, et al: Changes in left ventricular volume, mass, and function during the development and regression of supraventricular—induced cardiomyopathy. Circulation 83:635–644, 1991.

    Article  PubMed  CAS  Google Scholar 

  19. Weber KT, Pick R, Silver MA, et al: Fibrillar collagen and remodelling of dilated canine left ventricle. Circulation 82:1387–1401, 1990.

    Article  PubMed  CAS  Google Scholar 

  20. Reilly CF, Tewksbury DA, Schechter NM, et al: Rapid conversion of angiotensin I to angiotensin II by neutrophil and mast cell proteinases. J Biol Chem 257:8619–8622, 1982.

    PubMed  CAS  Google Scholar 

  21. Okunishi H, Miyazaki M, Toda N: Evidence for a putatively new angiotensin II generating enzyme in the vascular wall. Hypertens 2:227–284, 1984.

    Google Scholar 

  22. Ondetti MA, Rubin B, Cushman DW: Design of specific inhibitors of angiotensin-converting enzyme: New class of orally active antihypertensive agents. Science 196:441–447, 1977.

    Article  PubMed  CAS  Google Scholar 

  23. Swartz SL, Williams GH: Angiotensin-converting enzyme inhibition and prostaglandins. Am J Cardiol 49:1405–1409, 1982.

    Article  PubMed  CAS  Google Scholar 

  24. Morice AA, Brown MJ, Lowry R, et al: Angiotensin-converting enzyme and the cough reflex. Lancet 2:1116–1118, 1987.

    Article  PubMed  CAS  Google Scholar 

  25. Ikeda M, Sasaguri M, Marutu H, et al: Formation of angiotensin II by tonin-inhibitor complex. Hypertension 11:63–70, 1988.

    Article  PubMed  CAS  Google Scholar 

  26. Wong PC, Price WA, Chiu AT, et al: Nonpeptide angiotensin II receptor antagonists. VIII characterization of functional antagonism displayed by DuP 753, an orally active antihypertensive agent. J Pharmacol Exp Ther 252:719–725, 1990.

    PubMed  CAS  Google Scholar 

  27. Wong PC, Price Jr WA, Wexler RR, et al: Nonpeptide angiotensin II receptor antagonists. Studies with EXP 9270 and DuP 753. Hypertension 15:823–834, 1990.

    Article  PubMed  CAS  Google Scholar 

  28. Wong PC, Price WA Jr, Chiu AT, et al: Hypotensive action of DuP 753, an angiotensin II antagonist, in spontaneously hypertensive rats. Nonpeptide angiotensin II receptor antagonists: X. Hypertension 15:459–468, 1990.

    Article  PubMed  CAS  Google Scholar 

  29. Wong PC, Price WA, Chiu AT, et al: Nonpeptide angiotensin II receptor antagonists IX. Antihypertensive activity in rats of DuP 753, an orally active antihypertensive agent. J Pharmacol Exp Ther 252:726–732, 1990.

    PubMed  CAS  Google Scholar 

  30. Raya TE, Fonken SJ, Lee RW, et al: Hemodynamic effects of direct angiotensin-II blockade compared to converting enzyme-inhibition in a rat model of heart failure. Am J Hypertens 4:S334–340, 1991.

    Google Scholar 

  31. Christen Y, Waeber B, Nussberger J, et al: Oral administration of DuP 753, a specific angiotensin II receptor antagonist, to normal male volunteers: Inhibition of pressor response to exogenous angiotensin I and II. Circulation 83:1333–1343, 1991.

    Article  PubMed  CAS  Google Scholar 

  32. Wood CE: ACTH, Cortisol, and renin responses to arterial hypotension in sheep. Am J Physiol 251:R18–22, 1986.

    PubMed  CAS  Google Scholar 

  33. Camargo CA, Dowdy AJ, Hancock EW, et al: Decreased plasma clearance and hepatic extraction of aldosterone in patients with heart failure. J Clin Invest 44:356–365, 1965.

    Article  PubMed  CAS  Google Scholar 

  34. Cuneo RC, Espiner EA, Nicholls MG, et al: Effect of physiological levels of atrial natriuretic peptide on hormone secretion: Inhibition of angiotensin-induced aldosterone secretion and renin release in normal man. J Clin Endocrinol Metab 66:1–8, 1987.

    Google Scholar 

  35. Wong PC, Price WA Jr, Chiu AT, et al: Nonpeptide angiotensin II receptor antagonists XL Pharmacology of EXP3174: An active metabolite of DuP 753, on orally active antihyperten sive agent. J Pharmacol Exp Ther 255:211–217, 1990.

    PubMed  CAS  Google Scholar 

  36. Xie MH, Liu FY, Wong PC, et al: Proximal nephron and renal effects of DuP 753, a nonpeptide angiotensin II receptor antagonist. Kidney Int 38:473–479, 1990.

    Article  PubMed  CAS  Google Scholar 

  37. Packer M, Lee WH, Medina N, et al: Functional renal insufficiency during long-term therapy with captopril and enalapril in severe chronic heart failure. Ann Intern Med 106:346–354, 1987.

    PubMed  CAS  Google Scholar 

  38. Kirchheim H, Ehmke H, Persson P: Physiology of the renal baroreceptor mechanism of renin release and its role in congestive heart failure. Am J Cardiol 62:68E–71E, 1988.

    Article  PubMed  CAS  Google Scholar 

  39. Nussberger J, Brunner DB, Waeber B, et al: In vitro renin inhibition to prevent generation of angiotensin during determination of angiotensin I and II. Life Sci 42:1683–1688, 1983.

    Article  Google Scholar 

  40. Urata H, Healy B, Stewart RW, et al: Angiotensin II receptors in normal and failing human hearts. J Clin Endocrinol Metab 69(l):54–66, 1989.

    Article  PubMed  CAS  Google Scholar 

  41. Wilson KM, Magargal W, Berecek KH: Long-term captopril treatment. Angiotensin II receptors and responses. Hypertension 11(2 Pt 2):I148–152, 1988.

    PubMed  CAS  Google Scholar 

  42. Bristow MR, Ginsburg R, Minobe W, et al: Decreased catecholamine sensitivity and β-ad-renergic receptor density in failing human heart. N Engl J Med 307:205–211, 1982.

    Article  PubMed  CAS  Google Scholar 

  43. Nazarali AJ, Gutkind JS, Correa FM, et al: Decreased angiotensin II receptors in subfornical organ of spontaneously hypertensive rats after chronic antihypertensive treatment with enalapril. Am J Hypertens 3:59–61, 1990.

    PubMed  CAS  Google Scholar 

  44. Wilson SK, Lynch DR, Ladenson PW: Angiotensin II and atrial natriuretic factor-binding sites in various tissues in hypertension: Comparative receptor localization and changes in different hypertension models in the rat. Endocrinology 124(6):2799–2808, 1989.

    Article  PubMed  CAS  Google Scholar 

  45. Dzau VJ, Hirsch AT: Emerging role of the tissue renin—angiotensin systems in congestive heart failure. Eur Heart J 11:65–71, 1990.

    Article  PubMed  CAS  Google Scholar 

  46. Schunkert H, Hirsch AT, Mankadi S, et al: Renal angiotensinogen gene expression in experimental heart failure: Effect of angiotensin converting-enzyme inhibition. Clin Res 37:584A, 1989.

    Google Scholar 

  47. Hostetter TH, Pfeffer JM, Pfeffer MA, et al: Cardiorenal hemodynamics and sodium excretion in rats with myocardial infarction. Am J Physiol 245:H98–103, 1983.

    PubMed  CAS  Google Scholar 

  48. Hirsch AT, Talsness C, Lage A, et al: The effect of experimental myocardial infarction and chronic captopril treatment on plasma and tissue angiotensin converting-enzyme activity (abstract). Clin Res 37:266A, 1989.

    Google Scholar 

  49. Lorell BH, Schunkert H, Grice WN, et al: Alteration in cardiac angiotensin converting enzyme activity in pressure overload hypertrophy (abstract). Circulation 80(Suppl II):II297 1989.

    Google Scholar 

  50. Dempsey PJ, McCallum ZT, Kent KM, et al: Direct myocardial effects of angiotensin II. Am J Physiol 220:477–481, 1971.

    PubMed  CAS  Google Scholar 

  51. Kobayashi M, Furukawa Y, Chiba S: Positive chronotopic and inotropic effects of angiotensin II in the dog heart. Eur J Pharmacol 50:17–25, 1978.

    Article  PubMed  CAS  Google Scholar 

  52. Van Zwieten PA, de Jonge A: Interaction between the adrenergic and renin—angiotensin—aldosterone systems. Postgrad Med J 62(Suppl l):23–27, 1986.

    PubMed  Google Scholar 

  53. Persson S: Endocrinology of cardiac failure. Pathophysiologic aspects: Haeodynamics. Acta Med Scand Suppl 707:7–14, 1986.

    PubMed  CAS  Google Scholar 

  54. Naftilan AJ, Pratt RJ, Eldridge CS, et al: Angiotensin II induces c-fos expression in smooth muscle via transcriptional control. Hypertension 13:706–711, 1989.

    Article  PubMed  CAS  Google Scholar 

  55. Tarazi RC, Fouad FM: Reversal of cardiac hypertrophy. Hypertension 6:III 140–145, 1984.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1994 Springer Science+Business Media New York

About this chapter

Cite this chapter

Fitzpatrick, M.A., Rademaker, M., Espiner, E.A. (1994). Angiotensin II Receptor Antagonism in an Ovine Model of Heart Failure Comparison with ACE and Renin Inhibition. In: Saavedra, J.M., Timmermans, P.B.M.W.M. (eds) Angiotensin Receptors. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2464-9_15

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-2464-9_15

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-6049-0

  • Online ISBN: 978-1-4615-2464-9

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics