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Counteracting Hypertension

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Science  01 Aug 2003:
Vol. 301, Issue 5633, pp. 569
DOI: 10.1126/science.301.5633.569c

Angiotensin II (Ang II), the product of sequential degradation of angiotensinogen by renin-and angiotensin-converting enzyme, has long been considered the primary effector of the renin-angiotensin system, which plays a key role in regulating blood pressure and thus is important in the pathogenesis of cardiovascular disease. Recent research, however, suggests that the peptide angiotensin-(1–7) [Ang-(1–7)], which is produced through an alternative pathway and has cardiovascular effects antagonistic to those of Ang II, may be a physiologically relevant effector, too.

Santos et al. propose the orphan guanine nucleotide-binding protein (G protein)- coupled receptor (GPCR) Mas as the functional receptor for Ang-(1–7). The authors used autoradiographic analysis to compare Ang II and Ang-(1–7) binding in kidney slices from wild-type and Mas-deficient mice. Specific Ang-(1–7) binding was not detected in the mutant mice, whereas specific Ang II binding was still present. Furthermore, Ang-(1–7) elicited arachidonic acid release from two cultured cell lines transfected with Mas and showed specific binding to Mas-transfected cells. Finally, Mas knockout mice lost the wild-type antidiuretic response to Ang-(1–7) after water loading, and aortic rings from the mutant mice lacked Ang-(1–7)-dependent relaxation. These data implicate Mas as a physiologically active receptor for Ang-(1–7) and a potential target in the treatment of cardiovascular disease. — EA

Proc. Natl. Acad. Sci. U.S.A. 100, 8258 (2003).

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