on January 7, 2008
Published online before print January 7, 2008, doi: 10.1161/HYPERTENSIONAHA.107.102764
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Submitted on October 10, 2007
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. * To whom correspondence should be addressed. E-mail: alenina{at}mdc-berlin.de.
Abstract—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 gp91phox 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.
Revised on November 6, 2007
Endothelial Dysfunction and Elevated Blood Pressure in Mas Gene-Deleted Mice
Ping Xu;
Key words: Mas-deficient mice • endothelial function • Ang-(1-7) • reactive oxygen species • NO
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