Central effects of angiotensin-(1-7)

Abstract

Angiotensin (Ang) (1-7) constitutes an important functional end-product of the renin-angiotensin system endogenously formed from Ang I or Ang II through the catalytic activity of angiotensin-converting enzyme (ACE) 2, prolyl endopeptidase, thimet oligopeptidase or neutral endopeptidase 24.11. Ang-(1-7) lacks the pressor, dipsogenic or stimulatory effect on aldosterone release characteristic of Ang II. In contrast, it produces vasodilation, natriuresis and diuresis and inhibits angiogenesis and cell growth. At the central level, Ang-(1-7) acts in sites involved in the control of cardiovascular function, thus contributing to blood pressure regulation. For instance, in contrast to Ang II, intracerebroventricular infusion of Ang-(1-7) has been shown to improve the baroreflex control of heart rate. In fact, endogenous Ang-(1-7) is involved in the improvement of baroreflex sensitivity observed in spontaneously hypertensive rats during central ACE inhibition suggesting that it may contribute to the beneficial effects of ACE inhibitors. In addition, Ang-(1-7) caused blood pressure reduction when it was injected into the nucleus tractus solitarii, caudal ventrolateral medulla, paraventricular nucleus and anterior hypothalamic area, while an increase in blood pressure was observed when the peptide was injected into the rostral ventrolateral medulla. The lowering blood pressure effect caused by Ang-(1-7) at the central level may result from its inhibitory activity on norepinephrine release. Taken together, these findings suggest that Ang-(1-7), acting at peripheral and central sites, plays an important role in the regulation of cardiovascular and renal function and in the pathophysiology of hypertension.