Endothelial dysfunction and elevated blood pressure in Mas gene-deleted mice

被引:155
作者
Xu, Ping [1 ]
Costa-Goncalves, Andrey C. [1 ,2 ]
Todiras, Mihail [1 ]
Rabelo, Luiza A. [2 ,3 ]
Sampaio, Walkyria O. [2 ]
Moura, Marina M. [2 ]
Santos, Sergio Sousa [2 ]
Luft, Friedrich C. [1 ,4 ]
Bader, Michael [1 ]
Gross, Volkmar [1 ]
Alenina, Natalia [1 ]
Santos, Robson A. S. [2 ]
机构
[1] Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany
[2] Univ Fed Minas Gerais, Dept Physiol & Biophys, Belo Horizonte, MG, Brazil
[3] Univ Fed Alagoas, Setor Fisiol & Farmacol, ICBS, Maceio, Brazil
[4] HELIOS Klin, Franz Volhard Clin, Charite, Fac Med, Berlin, Germany
关键词
Mas-deficient mice; endothelial function; Ang-(1-7); reactive oxygen species; NO;
D O I
10.1161/HYPERTENSIONAHA.107.102764
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
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.
引用
收藏
页码:574 / 580
页数:7
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