Of the active fragments studied to-date, Ang-(1-7) is the most pleiotropic
of the Ang I metabolities because it exerts effects that may be identical o
r opposite to those of Ang II. While much research remains to be done, accu
mulating evidence suggests that Ang-(1-7) stimulates the synthesis and rele
ase of vasodilator prostaglandins, augments the metabolic actions of bradyk
inin, and increases the release of nitric oxide, This explains why Ang-(1-7
) activates antihypertensive mechanisms, particularly in situations of incr
eased Ang II activity. In other words, Ang-(1-7) may act as a negative feed
back hormone of the presser and trophic actions of Ang II. The enzymes form
ing Ang-(1-7) reinforce the idea that this peptide is a component of a vaso
depressor system that regulates blood pressure. Both neprilysin and metallo
endopeptidase 24.15 form Ang-(1-7) but also cleave bradykinin and atrial na
triuretic peptide to smaller fragments. Our recent discovery that Ang-(1-7)
is a major substrate for angiotensin converting enzyme (ACE) adds a new an
d important dimension to the understanding of the biochemical physiology of
the renin angiotensin system. Moreover, these data explain why Ang-(1-7) a
ugmentes the hypotensive effects of bradykinin and contributes to the antih
ypertensive actions of ACE inhibitors. While the bulk of the research in hy
pertension continues to emphasize the investigation of the cellular actions
of Ang II, our research has introduced new concepts and uncovered new mech
anisms through which angiotensin peptides control homeostasis and influence
the pathogenesis of cardiovascular disease.