Aldosterone Induces Superoxide Generation via Rac1 Activation in Endothelial Cells

Abstract

Currently, aldosterone is believed to be involved in the development of cardiovascular injury as a potential cardiovascular risk hormone. However, its exact cellular mechanisms remain obscure. This study was undertaken to examine the effect of aldosterone on superoxide production in cultured rat aortic endothelial cells with possible involvement of the small GTP-binding (G) protein Rac1. The aldosterone levels showed a time-dependent (6-24 h) and dose-dependent (10(-8) to 10(-6) m) increase in superoxide generation, whose effect was abolished by mineralocorticoid receptor antagonist (eplerenone), Src inhibitor (PP2), and reduced nicotinamide adenine dinucleotide phosphate [NAD(P)H] oxidase inhibitor (apocynin). Aldosterone activated NADP(H) oxidase and Rac1, whose effects were abolished by eplerenone. The aldosterone-induced superoxide generation was abolished either by nonselective small G protein inhibitor (Clostridium difficile toxin A) or dominant-negative Rac1. Dominant-negative Rac1 also inhibited aldosterone-induced ACE gene expression. 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.

Effect of morin, a flavonoid against DOCA-salt hypertensive rats: a dose dependent study

“…In addition, increased aldosterone concentrations may activate oxidative stress through an unregulated NADPH oxidase in the DOCA-salt model [35] . In agreement with previous report [25] we also observed that systolic and diastolic blood pressure was considerably increased in DOCA-salt hypertensive rats (group 3), which might be due to increased oxidative stress and decreased bioavailability of nitric oxide.…”

Role of mineralocorticoid receptor on atrial structural remodeling and inducibility of atrial fibrillation in hypertensive rats

“…Of note, it has also been demonstrated that aldosterone increased ACE gene expression in cardiovascular tissue via Rac1 dependent mechanisms. 22 Surprisingly, the beneficial effects of EPL on both atrial structural remodeling and the inducibility of AF were demonstrated in high blood pressure status. Of note, both increased ROS production assessed by HNE staining and activated Rac1 expression in DS+HS group were attenuated by EPL treatment only in LA, but not in LV.…”

“…19,20 Recently, some reports have revealed the relationship between MR activation and Rac1 activity. 21,22 However, little is known about the relationship between MR and Rac1 in the heart.…”

Pressure activates colon cancer cell adhesion via paxillin phosphorylation, Crk, Cas, and Rac1

“…Rac1 binds to Cas, although Rac1 also binds to and is activated by RhoG and aldosterone in other settings [58,59]. We hypothesized that paxillin-Crk-Cas interaction might influence Rac1.…”