title: Selective cerebral vascular dysfunction in Mn-SOD-deficient mice.
abstract: We tested the hypothesis that the mitochondrial form of superoxide dismutase [manganese superoxide dismutase (Mn-SOD)] protects the cerebral vasculature. Basilar arteries (baseline diameter approximately 140 microm) from mice were isolated, cannulated, and pressurized to measure vessel diameter. In arteries from C57BL/6 mice preconstricted with U-46619, acetylcholine (ACh; an endothelium-dependent vasodilator) produced dilation that was similar in male and female mice and abolished by an inhibitor of nitric oxide synthase. Vasodilation to ACh was not altered in heterozygous male or female Mn-SOD-deficient (Mn-SOD+/-) mice compared with wild-type littermate controls (Mn-SOD+/+). Constriction of the basilar artery to arginine vasopressin, but not KCl or U-46619, was increased in Mn-SOD+/- mice (P<0.05), and this effect was prevented by tempol, a scavenger of superoxide. We also examined responses of cerebral (pial) arterioles (branches of the middle cerebral artery, control diameter approximately 30 microm) to ACh in anesthetized mice using a cranial window. Responses to ACh, but not nitroprusside (an endothelium-independent agonist), were reduced (P<0.05) in cerebral arterioles in Mn-SOD+/- mice, and this effect was prevented by tempol. Thus these are the first data on the role of Mn-SOD in cerebral circulation. In the basilar artery, ACh produced nitric oxide-mediated dilation that was similar in male and female mice. Under normal conditions in cerebral arteries, responses to ACh were not altered but constrictor responses were selectively enhanced in Mn-SOD+/- mice. In the cerebral microcirculation, there was superoxide-mediated impairment of responses to ACh.
authors.affiliation: Department of Internal Medicine, E318-2-GH Carver College of Medicine, University of Iowa, Iowa City, IA 52242-1081, USA. frank-faraci@uiowa.edu
authors.forename: F M
authors.initials: FM
authors.lastname: Faraci
authors.forename: M L
authors.initials: ML
authors.lastname: Modrick
authors.forename: C M
authors.initials: CM
authors.lastname: Lynch
authors.forename: L A
authors.initials: LA
authors.lastname: Didion
authors.forename: P E
authors.initials: PE
authors.lastname: Fegan
authors.forename: S P
authors.initials: SP
authors.lastname: Didion
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001127:Arginine Vasopressin / Q000494:pharmacology; D001488:Basilar Artery / Q000187:drug effects / Q000503:physiopathology*; D002536:Cerebral Arteries / Q000187:drug effects / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000502:physiology*; D003497:Cyclic N-Oxides / Q000494:pharmacology; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009599:Nitroprusside / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000235:genetics / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D003497:Cyclic N-Oxides; D013113:Spin Labels; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D001127:Arginine Vasopressin; D009599:Nitroprusside; D011189:Potassium Chloride; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D013482:Superoxide Dismutase; D000109:Acetylcholine; C001803:tempol