Epidermal Growth Factor Receptor Is Critical For Angiotensin II-Mediated Hypertrophy in Cerebral Arterioles [Renin-Angiotensin System]

We examined the molecular mechanism of Ang II–mediated cerebrovascular remodeling that involves the epidermal growth factor receptor (EGFR) pathway. Mutant EGFR mice (waved-2), their heterozygous control (wild-type [WT]), and C57BL/6J mice were infused with Ang II (1000 ng kg–1 min–1) or saline via osmotic minipumps for 28 days (n=8 per group). Eight of the Ang II–infused C57BL/6J mice were cotreated with AG1478 (12 mg/kg per day, IP), a specific EGFR tyrosine kinase inhibitor. Systolic arterial pressure was measured by a tail-cuff method. Pressure and diameter of cerebral arterioles were measured through an open cranial window in anesthetized mice. Cross-sectional area of the wall was determined in pressurized fixed cerebral arterioles. Expression of phosphorylated EGFR (p-EGFR), caveolin-1 (Cav-1), and c-Src was determined by western blotting and immunohistochemistry. Mutation of EGFR or AG1478 treatment did not affect Ang II–induced hypertension. Ang II increased the expression of p-EGFR in WT mice, confirming the activation of EGFR. Ang II induced hypertrophy and inward remodeling of cerebral arterioles in WT mice. Hypertrophy, but not remodeling, was prevented in waved-2 and AG1478-treated C57BL/6J mice. Ang II increased p-EGFR, Cav-1, and c-Src expression in WT but not in waved-2 or AG1478-treated C57BL/6J mice. These results suggest that Ang II–induced hypertrophy in cerebral arterioles involves EGFR-dependent signaling and may inclu...
Source: Hypertension - Category: Cardiology Authors: Tags: Cerebrovascular disease/stroke, Hypertrophy, Other Vascular biology Renin-Angiotensin System Source Type: research