THURSDAY, Dec. 20 (HealthDay News) -- The ability of aldosterone to generate superoxide and cause cardiovascular injury is mediated by several cellular mediators including NAD(P)H oxidase and Rac1, according to a study published online Dec. 13 in Endocrinology.
Fumiko Iwashima, and colleagues from Tokyo Medical and Dental University Graduate School in Japan, examined the cellular mechanism underlying aldosterone's ability to generate superoxide in cultured rat aortic endothelial cells.
The researchers found that aldosterone increased superoxide production in a time- and dose-dependent manner, which was blocked by inhibitors of the mineralocorticoid receptor, the Src protein, or NAD(P)H oxidase. Aldosterone activated NAD(P)H oxidase and the small GTP-binding protein Rac1, which was blocked by a mineralocorticoid receptor inhibitor. Inhibiting Rac1 abolished the aldosterone induction of superoxide and expression of angiotensin-converting enzyme.
"Thus, the present study is the first to demonstrate that aldosterone induces superoxide generation via mineralocorticoid receptor-mediated activation of NAD(P)H-oxidase and Rac1 in endothelial cells, thereby contributing to the development of aldosterone-induced vascular injury," Iwashima and colleagues conclude.
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