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(Hypertension. 2008;51:574.)
© 2008 American Heart Association, Inc.

Original Articles Part 2

Endothelial Dysfunction and Elevated Blood Pressure in Mas Gene-Deleted Mice

Ping Xu; Andrey C. Costa-Goncalves; Mihail Todiras; Luiza A. Rabelo; Walkyria O. Sampaio; Marina M. Moura; Sergio Sousa Santos; Friedrich C. Luft; Michael Bader; Volkmar Gross; Natalia Alenina; Robson A.S. Santos

From the Max-Delbrück-Center for Molecular Medicine (P.X., A.C.C-G., M.T., F.C.L., M.B., V.G., N.A.), Berlin, Germany; the Department of Physiology and Biophysics (A.C.C-G., L.A.R., W.O.S., M.M.M., S.S.S., R.A.S.S.), Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; Setor de Fisiologia e Farmacologia (L.A.R.), Instituto de Ciências Biológicas e da Saúde (ICBS), Universidade Federal de Alagoas, Maceió, Brazil; and the Medical Faculty of the Charité (F.C.L.), Franz Volhard Clinic, HELIOS Klinikum, Berlin, Germany.

Correspondence to Natalia Alenina, Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Str 10, D-13125 Berlin-Buch, Germany. E-mail alenina{at}mdc-berlin.de

Mas codes for a G protein–coupled receptor that is implicated in angiotensin-(1-7) signaling. We studied the cardiovascular phenotype of Mas-deficient mice backcrossed onto the FVB/N genetic background using telemetry and found that they exhibit higher blood pressures compared with controls. These Mas^–/– mice also had impaired endothelial function, decreased NO production, and lower endothelial NO synthase expression. Reduced nicotinamide-adenine dinucleotide phosphate oxidase catalytic subunit gp91^phox protein content determined by Western blotting was higher in Mas^–/– mice than in controls, whereas superoxide dismutase and catalase activities were reduced. The superoxide dismutase mimetic, Tempol, decreased blood pressure in Mas^–/– mice but had a minimal effect in control mice. Our results show a major cardiovascular phenotype in Mas^–/– mice. Mas-deletion results in increased blood pressure, endothelial dysfunction, and an imbalance between NO and reactive oxygen species. Our animals represent a promising model to study angiotensin-(1-7)–mediated cardiovascular effects and to evaluate Mas agonistic compounds as novel cardioprotective and antihypertensive agents based on their beneficial effects on endothelial function.

Key Words: Mas-deficient mice • endothelial function • Ang-(1-7) • reactive oxygen species • NO