Role Of Caveolin‐1 In Signaling Pathways Involved In Angiotensin II‐Induced Activation Of Cerebral Vascular Hypertrophy And Remodeling

Abstract

Angiotensin II (Ang II) is a major determinant of vascular remodeling and hypertrophy in the cerebral circulation during chronic hypertension, which presumably plays an important role in production of stroke. We previously examined the effects of Caveolin‐1 (Cav1) on Ang II‐induced structural alterations in cerebral arterioles and found that deficiency of Cav1 prevented cerebral arteriolar remodeling and hypertrophy. The goal of this study was to examine the signaling pathways initiated by Cav1 during Ang II‐mediated cerebrovascular changes. Cav1 deficient (Cav1‐/‐) and B6129SF2/J wild type (WT) mice were infused with either Ang II (1000 ng/kg/day) or saline via osmotic minipumps for 28 days. Systolic arterial pressure (SAP) was measured by a tail‐cuff method. Expression of Cav1, p‐EGFR and p‐Akt was determined in cerebral arteries by western blotting and in cerebral arterioles by immunohistochemistry. Infusion of Ang II significantly increased SAP in both WT (149±3 vs 119±4 mmHg in saline infused, P<0.05) and Cav1‐/‐ mice (147±2 vs 108±5 mmHg, P<0.05), thus deficiency of Cav1 did not affect Ang II‐induced hypertension. Ang II increased expression of Cav1 in cerebral arteries and arterioles in WT mice, confirming that Ang II stimulated activation of Cav1. Further more Ang II stimulated EGFR transactivation and phosphorylation of Akt expression significantly (P<0.05) in cerebral arterioles in WT, but not in Cav1‐/‐ mice. These results suggest that Cav1 participates in Ang II stimulated transactivation of EGFR and Akt, both of which may play important roles in Ang II‐induced vascular hypertrophy and inward remodeling.