Endothelial dysfunction and elevated blood pressure in MAS gene-deleted mice
Authors
- P. Xu
- A.C. Costa-Goncalves
- M. Todiras
- L.A. Rabelo
- W.O. Sampaio
- M.M. Moura
- S.S. Santos
- F.C. Luft
- M. Bader
- V. Gross
- N. Alenina
- R.A.S. Santos
Journal
- Hypertension
Citation
- Hypertension 51 (2): 574-580
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.