Brain Renin–Angiotensin System in Hypertension, Cardiac Hypertrophy, and Heart Failure

Abstract

Brain renin–angiotensin system (RAS) is significantly involved in the roles of the endocrine RAS in cardiovascular regulation. Our studies indicate that the brain RAS participates in the development of cardiac hypertrophy and fibrosis through sympathetic activation. Inhibition of sympathetic hyperactivity after myocardial infarction through suppression of the brain RAS appears beneficial. Furthermore, the brain RAS modulates the cardiovascular and fluid–electrolyte homeostasis not only by interacting with the autonomic nervous system but also by modulating hypothalamic–pituitary axis and vasopressin release. The brain RAS is also involved in the modulation of circadian rhythms of arterial pressure, contributing to non-dipping hypertension. We conclude that the brain RAS in pathophysiological states interacts synergistically with the chronically overactive RAS through a positive biofeedback in order to maintain a state of alert in diseased conditions, such as cardiac hypertrophy and failure. Therefore, targeting brain RAS with drugs such as renin or angiotensin converting enzyme inhibitors or receptor blockers having increased brain penetrability could be of advantage.

The Angiotensin-Melatonin Axis

“…To test this hypothesis, we studied a transgenic rat that has reduced angiotensinogen levels in the brain through expression of an antisense RNA against angiotensinogen, induced by means of the astrocyte-specific glial fibrillary acidic protein promoter [32]. Ang II infusion in the TGR(ASrAOGEN) transgenic rats did not induce a BP circadian shift, indicating that peripheral RAS interacts with the brain RAS to induce not only hypertension [2] but also a BP circadian shift [15, 16]. We employed the TGR(ASrAOGEN) to investigate if the brain RAS is involved in circadian rhythm reentrainment to light phase shifts.…”

Contribution of the renin–angiotensin system in chronic foot-shock induced hypertension in rats

“…Among the effector peptides of the brain RAS, angiotensin (Ang) II and Ang III displayed similar affinities for the AT1 and AT2 receptors. Both peptides are involved in blood-pressure control and body fluid and electrolyte balance through interaction with AT1 receptors in the brain [3]. Previous studies have demonstrated that Ang II participated in foot-shock-stress-induced high blood pressure via stimulating hypothalamic vasopressin synthesis and release [14,25].…”

Neuropathic pain-attenuating potential of aliskiren in chronic constriction injury model in rats

“…Studies have shown the usefulness of renin inhibitors in hypertension, atherosclerosis, chronic kidney disease, cardiac hypertrophy and vascular inflammation. [10][11][12][13] In our previous studies, it was demonstrated that spironolactone (an aldosterone antagonist) and telmisartan (AT1 receptor antagonist) possess the ameliorative potential for attenuating neuropathic pain manifestations in a chronic constriction injury (CCI) model. 14,15 Since both aldosterone and AT1 receptors are part of the renin-angiotensin-aldosterone system, it is hypothesized that blocking the reninangiotensin-aldosterone system at a very early stage by directly inhibiting renin with aliskiren may also attenuate neuropathic pain in CCI.…”