title: 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.
  
  
  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.
authors.affiliation: Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: J B
authors.initials: JB
authors.lastname: Laursen
authors.forename: S
authors.initials: S
authors.lastname: Rajagopalan
authors.forename: Z
authors.initials: Z
authors.lastname: Galis
authors.forename: M
authors.initials: M
authors.lastname: Tarpey
authors.forename: B A
authors.initials: BA
authors.lastname: Freeman
authors.forename: D G
authors.initials: DG
authors.lastname: Harrison
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000804:Angiotensin II; D000818:Animals; D001011:Aorta / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000378:metabolism; D004337:Drug Carriers; D006973:Hypertension / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology*; D008081:Liposomes; D008264:Macrophages / Q000473:pathology; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*; D014664:Vasodilation
chemical_list: D004337:Drug Carriers; D008081:Liposomes; D013481:Superoxides; D000804:Angiotensin II; D009599:Nitroprusside; D013482:Superoxide Dismutase; D000109:Acetylcholine; D009638:Norepinephrine