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

Area of Science:

• Cardiovascular Physiology
• G protein-coupled receptor signaling

Background:

• The Mas receptor is a G protein-coupled receptor involved in angiotensin-(1-7) signaling.
• Dysregulation of this pathway is linked to cardiovascular diseases.

Purpose of the Study:

• To investigate the cardiovascular phenotype of Mas-deficient mice.
• To explore the role of the Mas receptor in blood pressure regulation and endothelial function.

Main Methods:

• Utilized telemetry to monitor blood pressure in Mas-deficient (Mas(-/-)) and control mice on an FVB/N background.
• Assessed endothelial function, nitric oxide (NO) production, and expression of related proteins (eNOS, gp91(phox)).
• Evaluated the effect of the superoxide dismutase mimetic, Tempol, on blood pressure.

Main Results:

• Mas(-/-) mice displayed significantly higher blood pressure compared to controls.
• Endothelial dysfunction, reduced NO production, and lower eNOS expression were observed in Mas(-/-) mice.
• Increased gp91(phox) protein and reduced antioxidant enzyme activities (SOD, catalase) were noted in Mas(-/-) mice.
• Tempol administration lowered blood pressure in Mas(-/-) mice but had minimal effect in controls.

Conclusions:

• Mas receptor deficiency leads to a pronounced cardiovascular phenotype, characterized by hypertension and endothelial dysfunction.
• An imbalance between NO and reactive oxygen species (ROS) contributes to the observed phenotype.
• Mas(-/-) mice serve as a valuable model for studying angiotensin-(1-7) effects and for developing Mas agonistic therapies for cardiovascular conditions.