A Role for Mas in Keeping Blood Pressure Down?

Science's STKE  22 Jul 2003:
Vol. 2003, Issue 192, pp. tw280-TW280
DOI: 10.1126/stke.2003.192.tw280

Angiotensin II (Ang II), the product of sequential degradation of angiotensinogen by renin and angiotensin-converting enzyme, has long been considered the effector of the renin-angiotensin system (RAS), which plays a key role in regulating blood pressure and thus 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 degradative pathway and has cardiovascular effects antagonistic to those of Ang II, may be a physiologically relevant effector of the RAS as well. Santos et al. implicated the orphan heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptor (GPCR) Mas as a functional receptor for Ang-(1-7), thus providing a molecular basis for Ang-(1-7) activity. The authors used autoradiographic analysis to compare Ang II and Ang-(1-7) binding to kidney slices from wild-type mice and mutant mice that lacked Mas. Specific Ang-(1-7) binding was eliminated in the Mas-deficient mice, whereas specific AngII binding was not affected. Ang-(1-7) elicited arachidonic acid release from Cos and Chinese hamster ovary cell lines transfected with Mas and showed specific binding to Mas-transfected cells. 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 thus open the door to new therapies for treating cardiovascular disease.

R. A. S. Santos, A. C. Simoes e Silva, C. Maric, D. M. R. Silva, R. P. Machado, I. de Buhr, S. Heringer-Walther, S. V. B. Pinheiro, M. T. Lopes, M. Bader, E. P. Mendes, V. S. Lemos, M. J. Campagnole-Santos, H.-P. Schultheiss, R. Speth, T. Walther, Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas. Proc. Natl. Acad. Sci. U.S.A. 100, 8258-8263 (2003). [Abstract] [Full Text]