Interactions between the sympathetic nervous system and the RAAS in heart failure

Abstract

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 beta-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 beta-adrenergic blockade may diminish activity of the RAAS. Conversely, angiotensin-converting 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.

RETRACTED: Angiotensin receptor blockade improves the net balance of cardiac Ca2+ handling-related proteins in sympathetic hyperactivity-induced heart failure

“…Heart failure is a progressive disorder that involves decreased cardiac output associated with neurohumoral activation (Goldsmith, 2004). It has been demonstrated that RAS and sympathetic nervous system over activation exert a direct deleterious effect on the heart, ultimately leading to cardiac dysfunction and pathological ventricular remodeling (Bacurau et al, 2009;Brum et al, 2002;Oliveira et al, 2009).…”

Exercise training reduces cardiac angiotensin II levels and prevents cardiac dysfunction in a genetic model of sympathetic hyperactivity-induced heart failure in mice

“…Neurohormonal mechanisms play a central role in the progression of HF by activating sympathetic nervous system and RAS (Goldsmith 2004;Mancia et al 2006;Zucker 2006). In fact, prolonged RAS and sympathetic nervous system hyperactivation in HF exerts a direct deleterious effect on the heart independently of their hemodynamic actions (Grassi et al 1997;Mann et al 1992).…”

Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system

“…Valsartan, an angiotensin receptor blocker, is able to simultaneously block signaling of both AT 1 Rs and ␤-adrenergic receptors in mice (11). Furthermore, beta-blockers have also been shown to interfere with ANG II signaling in heart failure and have become a mainstay of therapy in patients with chronic heart failure (11,56). The mechanisms and functional consequences of AT 1 R oligomerization remain elusive, but may provide a way to expand our pharmacologic armamentarium against vascular disease.…”