The central renin–angiotensin system and sympathetic nerve activity in chronic heart failure

Abstract

Chronic heart failure (CHF) is a multi-factorial disease process that is characterized by over activation of the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system. Both of these systems are chronically activated in CHF. The RAAS consists of an excitatory arm involving Angiotensin II (Ang II), Angiotensin Converting Enzyme (ACE), and the Ang II type 1 Receptor (AT1R). The RAAS also consists of a protective arm consisting of Angiotensin-1-7 (Ang -1-7), the Ang II type 2 receptor (AT2R), ACE2 and the mas receptor. Sympathoexcitation in CHF is driven, in large part, by an imbalance of these two arms, with an increase in the Ang II-AT1R-ACE arm and a decrease in the AT2R-ACE2 arm. This imbalance is manifested in cardiovascular-control regions of the brain such as the rostral ventrolateral medulla and paraventricular nucleus in the hypothalamus. This review focuses on current literature that describes the components of these two arms of the RAAS, and their imbalance in the CHF state. Moreover, this review provides additional evidence for the relevance of ACE2 and Ang-1-7 as key players in the regulation of central sympathetic outflow in CHF. Finally we also examine the effects of exercise training as a therapeutic strategy and the molecular mechanisms at play in CHF, in part, because of the ability of exercise training to restore the balance of the RAAS axis and sympathetic outflow.

Beneficial effects of adaptive servo-ventilation therapy on albuminuria in patients with heart failure

“…One possible cause of albuminuria in HF patients may be vascular inflammation induced by increased sympathetic nerve activity. Elevated sympathetic nerve activity activates the RAS system [10], induces bone marrow inflammatory cells [11], and leads to vascular remodeling events such as vasoconstriction, proliferation of vascular smooth muscle cells, and vascular inflammation. The present study showed that ASV-mediated changes in hs-CRP levels were significantly correlated with the changes in UACR in HF patients (Fig.…”

Circulating angiotensin II deteriorates left ventricular function with sympathoexcitation via brain angiotensin II receptor

“…2003), and AT 1 R signaling is mediated by a positive feedback of AT 1 R on the transcriptional regulation of the protein in the brain (Zucker et al. 2014). It has also been demonstrated that angiotensinergic sympathoexcitatory pathways project from the SFO to the paraventricular nucleus (PVN) in the hypothalamus, and from the PVN project to the RVLM (Wright et al.…”

Emerging role of hydrogen sulfide-microRNA crosstalk in cardiovascular diseases

“…An initial response to elevated blood pressure is activation of the renin angiotensin aldosterone system (RAAS) (124,167). However, chronic activation of the RAAS leads to heart failure (98,167). H 2 S inhibits activation of the RAAS in Dahl rats fed with a high-salt diet, mitigating hypertension (59).…”

“…Chronic high blood pressure creates excessive stress on the vasculature, leading to cardiac hypertrophy over time. An initial response to elevated blood pressure is activation of the renin angiotensin aldosterone system (RAAS) (124,167). However, chronic activation of the RAAS leads to heart failure (98,167).…”