Angiotensin-(1-7): a bioactive fragment of the renin-angiotensin system

Accumulating evidence suggests that angiotensin-(1-7) [Ang-(1-7)] is an imp ortant component of the renin-angiotensin system. As the most pleiotropic m etabolite of angiotensin I (Ang I) it manifest actions which are most often the opposite of those described for angiotensin II (Ang II). Ang-(1-7) is produced from Ang I bypassing the prerequisite formation of Ang II. The gen eration of Ang-(1-7) is under the control of at least three enzymes, which include neprilysin, thimet oligopeptidase, and prolyl oligopeptidase depend ing on the tissue compartment. Both neprilysin and thimet oligopeptidase ar e also involved in the metabolism of bradykinin and the atrial natriuretic peptide. Moreover, recent studies suggest that in addition to Ang I and bra dykinin, Ang-(1-7) is an endogenous substrate for angiotensin converting en zyme. This suggests that there is a complex relationship between the enzyma tic pathways forming angiotensin IT and other various vasodepressor peptide s from either the renin-angiotensin system or other peptide systems. The an tihypertensive actions of angiotensin-(1-7) are mediated by an angiotensin receptor that is distinct from the pharmacologically characterized AT, or A T, receptor subtypes. Ang-(1-7) mediates it antihypertensive effects by sti mulating synthesis and release of vasodilator prostaglandins, and nitric ox ide and potentiating the hypotensive effects of bradykinin. (C) 1998 Publis hed by Elsevier Science B.V. All rights reserved.