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 eit her identical to or opposite that of angiotensin II. Angiotensin I can be directly converted to angiotensin-(1-7), bypassing formation of an giotensin II. This pathway is under the control of three enzymes: neut ral endopeptidases 24.11 (neprilysin) and 24.15 and prolyl-endopeptida se 24.26. Two of the three angiotensin-forming enzymes (neprilysin and endopeptidase 24.15) also contribute to the breakdown of bradykinin a nd 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 pept ides are intertwined through this enzymatic pathway. Substantial evide nce suggests that angiotensin-(1-7) stimulates the synthesis and relea se of vasodilator prostaglandins, and nitric oxide, while also augment ing 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. T hese physiologic effects of angiotensin-(1-7) favor a blood pressure-l owering effect. The majority of the data currently available suggest t hat an,angiotensin-(1-7) mediates its effects through a novel non-AT(1 )/AT(2) receptor subtype.