title: Endothelial dysfunction and elevated blood pressure in MAS gene-deleted mice.
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 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.
authors.affiliation: Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Str 10, D-13125 Berlin-Buch, Germany.
authors.forename: Ping
authors.initials: P
authors.lastname: Xu
authors.forename: Andrey C
authors.initials: AC
authors.lastname: Costa-Goncalves
authors.forename: Mihail
authors.initials: M
authors.lastname: Todiras
authors.forename: Luiza A
authors.initials: LA
authors.lastname: Rabelo
authors.forename: Walkyria O
authors.initials: WO
authors.lastname: Sampaio
authors.forename: Marina M
authors.initials: MM
authors.lastname: Moura
authors.forename: Sergio Sousa
authors.initials: SS
authors.lastname: Santos
authors.forename: Friedrich C
authors.initials: FC
authors.lastname: Luft
authors.forename: Michael
authors.initials: M
authors.lastname: Bader
authors.forename: Volkmar
authors.initials: V
authors.lastname: Gross
authors.forename: Natalia
authors.initials: N
authors.lastname: Alenina
authors.forename: Robson A S
authors.initials: RA
authors.lastname: Santos
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001011:Aorta / Q000378:metabolism; D001682:Biological Availability; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D008297:Male; D008562:Membrane Glycoproteins; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D010641:Phenotype; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000172:deficiency*; D017382:Reactive Oxygen Species / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency*; D013113:Spin Labels; D014664:Vasodilation
chemical_list: D000975:Antioxidants; D003497:Cyclic N-Oxides; D008562:Membrane Glycoproteins; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D017382:Reactive Oxygen Species; D043562:Receptors, G-Protein-Coupled; D013113:Spin Labels; D009569:Nitric Oxide; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C001803:tempol