Novel angiotensin peptides regulate blood pressure, endothelial function, and natriuresis.
Accumulating evidence suggests that angiotensin-(1-7) is an important component of the renin-angiotensin system, having actions that are either identical to or opposite that of angiotensin II. Angiotensin I can be directly converted to angiotensin-(1-7), bypassing formation of angiotensin II. This pathway is under the control of three enzymes: neutral endopeptidases 24.11 (neprilysin) and 24.15 and prolyl-endopeptidase 24.26. Two of the three angiotensin-forming enzymes (neprilysin and endopeptidase 24.15) also contribute to the breakdown of bradykinin and the atrial natriuretic peptide. Furthermore, angiotensin-(1-7) is a major substrate for angiotensin-converting enzyme. These observations suggest that the process of biotransformation between the various Ang peptides of the renin-angiotensin system and other vasodepressor peptides are intertwined through this enzymatic pathway. Substantial evidence suggests that angiotensin-(1-7) stimulates the synthesis and release of vasodilator prostaglandins, and nitric oxide, while also augmenting the metabolic actions of bradykinin. In addition, angiotensin-(1-7) alters tubular sodium and bicarbonate reabsorption, decreases Na+-K+-ATPase activity, induces diuresis, and exerts a vasodilator effect. These physiologic effects of angiotensin-(1-7) favor a blood pressure-lowering effect. The majority of the data currently available suggest that angiotensin-(1-7) mediates its effects through a novel non-AT1/AT2 receptor subtype.
Ferrario
C M
CM
The Hypertension and Vascular Disease Center, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1032, USA.
Chappell
M C
MC
Dean
R H
RH
Iyer
S N
SN
D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000201:enzymology*; D006801:Humans; D009318:Natriuresis / Q000502:physiology*; D051381:Rats; D012016:Reference Values; D012084:Renin-Angiotensin System / Q000502:physiology*
D000804:Angiotensin II