Cerebrovascular oxidative stress and endothelial dysfunction in response to aldosterone is Nox2‐mediated

Abstract

Aldosterone is thought to be an important contributor to hypertension. There is an association between high aldosterone levels and stroke risk that is blood pressure‐independent. High aldosterone levels may increase stroke risk through effects on the cerebral vasculature involving oxidative stress (via Nox2‐oxidase) and endothelial dysfunction. We tested whether aldosterone produces cerebrovascular oxidative stress and endothelial dysfunction, and Nox2‐oxidase involvement. Aldosterone treatment (0.28 mg/kg/day, 2 wks) had no effect on blood pressure. Aldosterone impaired dilation of isolated, pressurised basilar arteries to acetylcholine (ACh; endothelium‐dependent agonist) compared to vehicle treatment in control mice, indicating aldosterone causes endothelial dysfunction. In contrast, aldosterone had no effect on ACh responses in Nox2‐deficient mice, indicating this effect is Nox2‐dependent. Basal and Nox2‐stimulated superoxide levels were greater in cerebral arteries of aldosterone vs vehicle‐treated mice, effects that were abolished in Nox2‐deficient mice. These data provide the first evidence suggesting aldosterone causes oxidative stress and endothelial dysfunction in brain via Nox2‐oxidase.