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

Ovid Technologies (Wolters Kluwer Health) - Tập 95 Số 3 - Trang 588-593 - 1997
Jørn Bech Laursen1, Sanjay Rajagopalan1, Zorina S. Galis1, Margaret M. Tarpey1, Bruce Α. Freeman1, David G. Harrison1
1the Department of Medicine, Cardiology Division, Emory University School of Medicine (J.B.L., S.R., Z.G., D.G.H.), Atlanta, Ga; the Atlanta (Ga) Veterans Administration Medical Center (D.G.H.); the Department of Anesthesiology (M.T., B.A.F.), University of Alabama at Birmingham; and Medical Department B, Division of Cardiology (J.B.L.), Rigshospitalet, Denmark.

Tóm tắt

Background The major source of superoxide (·O 2 − ) 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 ·O 2 − 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 ·O 2 − 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 ·O 2 − 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 ·O 2 − , likely via degradation of endothelium-derived NO·. Increased vascular ·O 2 − may contribute to vascular disease in high renin/angiotensin II states.

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Ovid Technologies (Wolters Kluwer Health)

Tập 95 Số 3

588-593

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