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.