Interactions between the sympathetic nervous system and the RAAS in heart failure
- Steven R. Goldsmith MD
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Therapy for heart failure caused by left ventricular systolic dysfunction is based on interference with maladaptive activation of the sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone system (RAAS). Agents that block β-adrenergic receptors, decrease angiotensin-II formation, and antagonize the effects of angiotensin II and aldosterone have been shown to improve morbidity and mortality in this syndrome. Therefore, from a theoretical point of view, it would be desirable to actually diminish the degree of overactivity of these two homeostatic systems. There are compelling physiologic arguments and much experimental data to suggest that β-adrenergic blockade may diminish activity of the RAAS. Conversely, angiotensinconverting enzyme inhibitors, angiotensin-II antagonists, and aldosterone antagonists may diminish activity of the SNS. Some clinical trials data may be interpreted in a fashion that suggests that part of the benefit of interfering with each system may relate to diminishing activity of the other. If true, combined therapy may lead to a virtuous cycle in which diminishing the adverse effects of each individual system is combined with reduced activity of the other. Such a cycle may be one factor underlying the impressive clinical results of recent neurohormonally based therapeutic trials and reinforces the need to look beyond acute hemodynamic effects of therapeutic agents when assessing their long-term impact in heart failure.
- The CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). N Engl J Med 1987, 316:1429–1435. CrossRef
- The SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med 1991, 325:293–302. CrossRef
- The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet 1999, 353:9–13.
- Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet 1999, 353:2001–2007.
- Cohn JN, Tognoni G: A randomized trial of the angiotensinreceptor blocker valsartan in chronic heart failure. N Engl J Med 2001, 345:1667–1675. CrossRef
- Pitt B, Zannad F, Remme WJ, et al.: The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med 1999, 341:709–717. CrossRef
- Packer M, Bristow M, Cohn JN, et al.: The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. N Engl J Med 1996, 334:1349–1355. CrossRef
- Packer M, Coats AJ, Fowler MB, et al.: Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med 2001, 344:1651–1658. CrossRef
- Pfeffer MA, Swedberg K, Granger CB, et al.: Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-overall programme. Lancet 2003, 362:759–766. CrossRef
- Goldsmith SR: Therapeutics in congestive heart failure: from hemodynamics to neurohormones. In Cardiac Remodeling and Failure. Edited by Singal P, Dixon I, Kirshenbaum LA, Dhalla N. Boston: Kluwer Academic Publishers; 2003:17–34. This is a thorough review of the past 20 years of pharmacologic treatment for heart failure, with an emphasis on how neurohormonally based therapy has supplanted therapy directed at hemodynamics. It also includes a discussion of the mechanisms of sympathoactivation in heart failure.
- Eichhorn EJ, Bristow MR: Medical therapy can improve the biological properties of the chronically failing heart. A new era in the treatment of heart failure. Circulation 1996, 94:2285–2296.
- Waagstein F, Hjalmarson A, Varnauskas E, Wallentin I: Effect of chronic beta-adrenergic receptor blockade in congestive cardiomyopathy. Br Heart J 1975, 37:1022–1036.
- Engelmeier RS, O’Connell JB, Walsh R, et al.: Improvement in symptoms and exercise tolerance by metoprolol in patients with dilated cardiomyopathy: a double-blind, randomized, placebo-controlled trial. Circulation 1985, 72:536–546.
- Cody RJ, Laragh JH: The renin-angiotensin-aldosterone system in chronic heart failure. In Drug Treatment of Heart Failure. Secaucus, NY: ATC; 1988:81. This is a thorough review of the role of the RAAS in heart failure, with therapeutic and mechanistic implications.
- Jorde UP, Ennezat PV, Lisker J, et al.: Maximally recommended doses of angiotensin-converting enzyme (ACE) inhibitors do not completely prevent ACE-mediated formation of angiotensin II in chronic heart failure. Circulation 2000, 101:844–846.
- Francis GS, Siegel RM, Goldsmith SR, et al.: Acute vasoconstrictor response to intravenous furosemide in patients with chronic congestive heart failure. Activation of the neurohumoral axis. Ann Intern Med 1985, 103:1–6.
- Campbell DJ, Aggarwal A, Esler M, Kaye D: Beta-blockers, angiotensin II, and ACE inhibitors in patients with heart failure. Lancet 2001, 358:1609–1610. This is a good discussion of the interaction of the various neurohormonal systems in clinical heart failure. CrossRef
- Cohn JN: Interaction of beta-blockers and angiotensin receptor blockers/ACE inhibitors in heart failure. J Renin Angiotensin Aldosterone Syst 2003, 4:137–139. CrossRef
- Pitt B, Remme W, Zannad F, et al.: Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003, 348:1309–1321. CrossRef
- Zucker IH, Wang W, Brandle M, et al.: Neural regulation of sympathetic nerve activity in heart failure. Prog Cardiovasc Dis 1995, 37:397–414. CrossRef
- Goldsmith SR: Angiotensin II and sympathoactivation in heart failure. J Card Fail 1999, 5:139–145. This is a thorough review of the effects of angiotensin II on sympathetic activity, with an emphasis on clinical relevance to heart failure. CrossRef
- Wang W, Zucker IH: Cardiac sympathetic afferent reflex in dogs with congestive heart failure. Am J Physiol 1996, 271:R751-R756.
- Ma R, Zucker IH, Wang W: Reduced NO enhances the central gain of cardiac sympathetic afferent reflex in dogs with heart failure. Am J Physiol 1999, 276:H19-H26.
- Clemson B, Gaul L, Gubin SS, et al.: Prejunctional angiotensin II receptors. Facilitation of norepinephrine release in the human forearm. J Clin Invest 1994, 93:684–691.
- Goldsmith SR, Hasking GJ: Subpressor infusions of angiotensin II do not stimulate sympathetic activity in humans. Am J Physiol 1990, 258:H179-H182.
- Goldsmith SR, Hasking GJ: Angiotensin II and sympathetic nervous activity in patients with congestive heart failure. J Am Coll Cardiol 1993, 21:1107–1113. CrossRef
- Goldsmith SR, Rector TS, Bank AJ, et al.: Effect of angiotensin II on noradrenaline release in the human forearm. Cardiovasc Res 1994, 28:663–666. CrossRef
- Goldsmith SR, Garr M, McLaurin M: Regulation of regional norepinephrine spillover in heart failure: the effect of angiotensin II and beta-adrenergic agonists in the forearm circulation. J Card Fail 1998, 4:305–310. CrossRef
- Goldsmith SR, Hasking GJ: Effect of a pressor infusion of angiotensin II on sympathetic activity and heart rate in normal humans. Circ Res 1991, 68:263–268.
- Murakami H, Liu JL, Zucker IH: Angiotensin II enhances (ibid.) baroreflex control of sympathetic outflow in heart failure. Hypertension 1997, 29:564–569.
- Kasama S, Toyama T, Kumakura H, et al.: Effect of spironolactone on cardiac sympathetic nerve activity and left ventricular remodeling in patients with dilated cardiomyopathy. J Am Coll Cardiol 2003, 41:574–581. CrossRef
- Grassi G, Cattaneo BM, Seravalle G, et al.: Effects of chronic ACE inhibition on sympathetic nerve traffic and baroreflex control of circulation in heart failure. Circulation 1997, 96:1173–1179. This is perhaps the key paper linking therapy with ACEI to diminished activity of the sympathetic nervous system in heart failure.
- Cohn JN, Johnson G, Ziesche S, et al.: A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure. N Engl J Med 1991, 325:303–310. CrossRef
- Francis GS, Cohn JN, Johnson G, et al.: Plasma norepinephrine, plasma renin activity, and congestive heart failure. Relations to survival and the effects of therapy in V-HeFT II. The V-HeFT VA Cooperative Studies Group. Circulation 1993, 87:VI40-VI48. This is a provocative analysis linking differential outcomes of therapies in the V-HEFT II trial to the effects of those therapies on plasma norepinephrine levels.
- Interactions between the sympathetic nervous system and the RAAS in heart failure
Current Heart Failure Reports
Volume 1, Issue 2 , pp 45-50
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- 1. Hennepin County Medical Center, 701 Park Avenue, 55415, Minneapolis, MN, USA