Interactions between the sympathetic nervous system and the RAAS in heart failure
- 154 Downloads
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.
Unable to display preview. Download preview PDF.
References and Recommended Reading
- 3.The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet 1999, 353:9–13.Google Scholar
- 4.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.Google Scholar
- 10.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.Google Scholar
- 14.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.Google Scholar
- 32.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.PubMedGoogle Scholar
- 34.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.PubMedGoogle Scholar