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HIGHLIGHTED TOPIC
Regulation of the Cerebral Circulation

Selective cerebral vascular dysfunction in Mn-SOD-deficient mice

Departments of ¹Internal Medicine and ²Pharmacology, Cardiovascular Center, Carver College of Medicine, University of Iowa, Iowa City, Iowa

Submitted 2 August 2005 ; accepted in final form 1 March 2006

We tested the hypothesis that the mitochondrial form of superoxide dismutase [manganese superoxide dismutase (Mn-SOD)] protects the cerebral vasculature. Basilar arteries (baseline diameter 140 µm) 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 30 µm) 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.

basilar artery; cerebral arterioles; endothelium; genetically altered mice; acetylcholine

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