Role of Superoxide in Angiotensin II–Induced but Not Catecholamine-Induced Hypertension

Abstract

Background The major source of superoxide (·O2−) in vascular tissues is an NADH/NADPH-dependent, membrane-bound oxidase. We have previously shown that this oxidase is activated in angiotensin II– but not norepinephrine-induced hypertension. We hypothesized that hypertension associated with chronically elevated angiotensin II might be caused in part by vascular ·O2− production. Methods and Results We produced hypertension in rats by a 5-day infusion of angiotensin II or norepinephrine. Rats were also treated with liposome-encapsulated superoxide dismutase (SOD) or empty liposomes. Arterial pressure was measured in conscious rats under baseline conditions and during bolus injections of either acetylcholine or nitroprusside. Vascular ·O2− production was assessed by lucigenin chemiluminescence. In vitro vascular relaxations were examined in organ chambers. Norepinephrine infusion increased blood pressure to a similar extent as angiotensin II infusion (179±5 and 189±4 mm Hg, respectively). In contrast, angiote...