The renin–angiotensin system in cardiovascular autonomic control: recent developments and clinical implications

Abstract

Complex and bidirectional interactions between the renin-angiotensin system (RAS) and autonomic nervous system have been well established for cardiovascular regulation under both physiological and pathophysiological conditions. Most research to date has focused on deleterious effects of components of the vasoconstrictor arm of the RAS on cardiovascular autonomic control such as renin, angiotensin II, and aldosterone. The recent discovery of prorenin and the prorenin receptor have further increased our understanding of RAS interactions in autonomic brain regions. Therapies targeting these RAS components, such as angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers, are commonly used for treatment of hypertension and cardiovascular diseases, with blood pressure lowering effects attributed in part to sympathetic inhibition and parasympathetic facilitation. In addition, a vasodilatory arm of the RAS has emerged that includes angiotensin-(1-7), ACE2, and alamandine and promotes beneficial effects on blood pressure in part by reducing sympathetic activity and improving arterial baroreceptor reflex function in animal models. The role of the vasodilatory arm of the RAS to cardiovascular autonomic regulation in clinical populations, however, has yet to be determined. This review will summarize recent developments in autonomic mechanisms involved in effects of the RAS on cardiovascular regulation, with a focus on newly discovered pathways and therapeutic targets for this hormonal system.

Identifying roles for peptidergic signaling in mice

“…This result suggested that other systems might be compensating for the low levels of ANP in Pam Myh6-cKO/cKO mice. The renin-angiotensin system increases blood pressure by stimulating the conversion of angiotensinogen to angiotensin I; renin secretion is stimulated by low blood sodium and sympathetic input and suppressed by ANP (56). However, assays for serum renin levels in WT and Pam Myh6-cKO/cKO mice on a normal salt diet revealed no difference (Fig.…”

Nervous system involvement after infection with COVID-19 and other coronaviruses

“…Angiotensin-converting enzyme 2 (ACE2) is a cardio-cerebral vascular protection factor existing in a variety of organs, including the nervous system and skeletal muscles, playing a major role in regulating blood pressure and anti-atherosclerosis mechanisms (Miller and Arnold, 2019). Meanwhile, ACE2 is also an important target for various CoV and influenza viruses (Turner et al, 2004;Wrapp et al, 2020;Yang et al, 2014).…”

Deleterious effects of viral pneumonia on cardiovascular system

“…Angiotensin-converting enzyme 2 can catalyse the conversion of angiotensin (Ang) II into Ang-(1-7), and the latter can act on the Mas receptor, then play a crucial role in cardiovascular protection, such as regulating blood pressure, anti-atherosclerosis, inhibiting fibrosis, and improving heart function. 56,57 Unexpectedly, ACE2 is also a vital target for a variety of coronaviruses and influenza viruses. 58,59 Liu et al 60 reported that the influenza neuraminidase of H1N1 viruses could directly cleave the ACE2 protein and then degrade it via proteasome pathway, so ACE2 protein levels were significantly down-regulated after being infected with H1N1 viruses.…”