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


  • 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


  • Hypertension


  • Hypertension 51 (2): 574-580


  • 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.