Angiotension-(1-7) and antihypertensive mechanisms.
Of the active fragments studied to-date, Ang-(l-7) is the most pleiotropic of the Ang I metabolities because it exerts effects that may be identical or opposite to those of Ang II. While much research remains to be done, accumulating evidence suggests that Ang-(1-7) stimulates the synthesis and release of vasodilator prostaglandins, augments the metabolic actions of bradykinin, and increases the release of nitric oxide. This explains why Ang-(1-7) activates antihypertensive mechanisms, particularly in situations of increased Ang II activity. In other words, Ang-(1-7) may act as a negative feedback hormone of the pressor and trophic actions of Ang II. The enzymes forming Ang-( 1-7) reinforce the idea that this peptide is a component of a vasodepressor system that regulates blood pressure. Both neprilysin and metalloendopeptidase 24.15 form Ang-(1-7) but also cleave bradykinin and atrial natriuretic peptide to smaller fragments. Our recent discovery that Ang-(1-7) is a major substrate for angiotensin converting enzyme (ACE) adds a new and important dimension to the understanding of the biochemical physiology of the renin angiotensin system. Moreover, these data explain why Ang-(1-7) augmentes the hypotensive effects of bradykinin and contributes to the antihypertensive actions of ACE inhibitors. While the bulk of the research in hypertension continues to emphasize the investigation of the cellular actions of Ang II, our research has introduced new concepts and uncovered new mechanisms through which angiotensin peptides control homeostasis and influence the pathogenesis of cardiovascular disease.
The Hypertension and Vascular Disease Center, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1032, USA. cferrari@bgsm.edu
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D000803:Angiotensin I / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D007668:Kidney / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology* / Q000502:physiology; D011945:Receptors, Angiotensin / Q000502:physiology
D000959:Antihypertensive Agents; D010446:Peptide Fragments; D011945:Receptors, Angiotensin; D000803:Angiotensin I; C118790:angiotensin I (1-7)