Endothelin-1 Stimulates Arterial VCAM-1 Expression Via NADPH Oxidase-Derived Superoxide in Mineralocorticoid Hypertension

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Abstract
Although hypertension is a major risk factor for atherosclerosis, its underlying mechanisms remain to be delineated. We have recently reported that both endothelin-1 (ET-1) and vascular cellular adhesion molecule-1 (VCAM-1) levels, key early markers of atherosclerosis, are significantly elevated in carotid arteries of deoxycorticosterone acetate (DOCA)-salt hypertensive rats, a model known for its suppressed plasma renin levels. This study tested the hypothesis that ET-1 augments arterial VCAM-1 expression through NADPH oxidase-derived superoxide (O2−). Carotid arteries of DOCA-salt or sham-operated rats were transduced ex vivo with extracellular superoxide dismutase (EC-SOD), dominant negative HA-tagged N17Rac1 that inhibits Rac1, the small GTPase component of NADPH oxidase, or β-galactosidase (β-gal) reporter gene (5×1010 plaque formation units [pfu]/mL), and the effect of transgene expression on O2− and VCAM-1 levels was assayed 24 hours afterward. The arterial activity of NADPH oxidase but not xanthin...