Role of superoxide in angiotensin II–induced but not catecholamine-induced hypertension
JB Laursen, S Rajagopalan, Z Galis, M Tarpey… - Circulation, 1997 - Am Heart Assoc
Circulation, 1997•Am Heart Assoc
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 …
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 …
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, angiotensin II–induced hypertension was associated with increased vascular ·O2− production, whereas norepinephrine-induced hypertension was not. Treatment with liposome-encapsulated SOD reduced blood pressure by 50 mm Hg in angiotensin II–infused rats while having no effect on blood pressure in control rats or rats with norepinephrine-induced hypertension. Similarly, liposome-encapsulated SOD enhanced in vivo hypotensive responses to acetylcholine and in vitro responses to endothelium-dependent vasodilators in angiotensin II–treated rats.
Conclusions Hypertension caused by chronically elevated angiotensin II is mediated in part by ·O2−, likely via degradation of endothelium-derived NO·. Increased vascular ·O2− may contribute to vascular disease in high renin/angiotensin II states.
Am Heart Assoc