NOX2 deficiency prevents angiotensin II‐induced hypertrophy and inward remodeling in cerebral arterioles

Abstract

We examined the role of NAD(P)H oxidase subunit NOX2 on structural alterations in cerebral arterioles induced by angiotensin II (Ang II). NOX2‐deficient (NOX2‐/‐) and wild‐type (WT) mice were infused with a pressor or a sub‐pressor dose of Ang II (1000 or 200 ng/kg/day) or saline via osmotic minipumps for 4 weeks. Systolic arterial pressure (SAP) was measured by a tail‐cuff method. Pressure and diameter of cerebral arterioles were measured via an open cranial window in anesthetized mice. In WT and NOX2‐/‐ mice, the pressor, but not the sub‐pressor, dose of Ang II increased SAP (135±5 vs 106±3 mmHg). Superoxide levels in cerebral arterioles (hydroethidine staining) were increased by both doses of Ang II in WT (staining density: 41±5 and 32±2 vs 18±5 %), but not in NOX2‐/‐ mice. The sub‐pressor, as well as the pressor, dose of Ang II significantly reduced external diameter of maximally dilated cerebral arterioles in WT mice (51±3 and 52±3 vs 58±2 μm at 30 mmHg), but not in NOX2‐/‐ mice. Cross‐sectional area (CSA) of the arteriolar wall was significantly increased in WT mice (497±58 vs 388±50 μm2) by the pressor, but not the sub‐pressor, dose of Ang II. In contrast, the pressor dose of Ang II did not increase CSA in NOX2‐/‐ mice. These findings suggest that generation of superoxide may play an important role in Ang II‐induced hypertrophy and inward remodeling in cerebral arterioles.