ROLE OF SUPEROXIDE IN ANGIOTENSIN-II-INDUCED BUT NOT CATECHOLAMINE-INDUCED HYPERTENSION

Background The major source of superoxide (. O-2(-)) in vascular tissu es is an NADH/NADPH-dependent, membrane-bound oxidase. We have previou sly shown that this oxidase is activated in angiotensin II- but not no repinephrine-induced hypertension. We hypothesized that hypertension a ssociated with chronically elevated angiotensin Il might be caused in part by vascular . O-2(-) production. Methods and Results We produced hypertension in rats by a 5-day infusion of angiotensin II or norepine phrine. Rats were also treated with liposome-encapsulated superoxide d ismutase (SOD) or empty liposomes. Arterial pressure was measured in c onscious rats under baseline conditions and during bolus injections of either acetylcholine or nitroprusside. Vascular . O-2(-) production w as assessed by lucigenin chemiluminescence. In vitro vascular relaxati ons 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-induce d hypertension was associated with increased vascular . O-2(-) product ion, whereas norepinephrine-induced hypertension was not. Treatment wi th liposome-encapsulated SOD reduced blood pressure by 50 mm Hg in ang iotensin II-infused rats while having no effect on blood pressure in c ontrol rats or rats with norepinephrine-induced hypertension. Similarl y, liposome-encapsulated SOD enhanced in vivo hypotensive responses to acetylcholine and in vitro responses to endothelium-dependent vasodil ators in angiotensin II-treated rats. Conclusions Hypertension caused by chronically elevated angiotensin II is mediated in part by . O-2(-) , likely via degradation of endothelium-derived NO .. Increased vascul ar . O-2(-) may contribute to vascular disease in high renin/angiotens in II states.