Angiotensin-(1-7) and antihypertensive mechanisms

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.