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Vasomotor responses in MnSOD-deficient mice

Departments of ¹Internal Medicine and ²Pharmacology, University of Iowa, Roy J. and Lucille A. Carver College of Medicine; and ³Veterans Administration Medical Center, Iowa City, Iowa 52242

Submitted 22 December 2003 ; accepted in final form 2 May 2004

MnSOD is the only mammalian isoform of SOD that is necessary for life. MnSOD^–/– mice die soon after birth, and MnSOD^+/– mice are more susceptible to oxidative stress than wild-type (WT) mice. In this study, we examined vasomotor function responses in aortas of MnSOD^+/– mice under normal conditions and during oxidative stress. Under normal conditions, contractions to serotonin (5-HT) and prostaglandin F₂ (PGF₂), relaxation to ACh, and superoxide levels were similar in aortas of WT and MnSOD^+/– mice. The mitochondrial inhibitor antimycin A reduced contraction to PGF₂ and impaired relaxation to ACh to a similar extent in aortas of WT and MnSOD^+/– mice. The Cu/ZnSOD and extracellular SOD inhibitor diethyldithiocarbamate (DDC) paradoxically enhanced contraction to 5-HT and superoxide more in aortas of WT mice than in MnSOD^+/– mice. DDC impaired relaxation to ACh and reduced total SOD activity similarly in aortas of both genotypes. Tiron, a scavenger of superoxide, normalized contraction to 5-HT, relaxation to ACh, and superoxide levels in DDC-treated aortas of WT and MnSOD^+/– mice. Hypoxia, which reportedly increases superoxide, reduced contractions to 5-HT and PGF₂ similarly in aortas of WT and MnSOD^+/– mice. The vasomotor response to acute hypoxia was similar in both genotypes. In summary, under normal conditions and during acute oxidative stress, vasomotor function is similar in WT and MnSOD^+/– mice. We speculate that decreased mitochondrial superoxide production may preserve nitric oxide bioavailability during oxidative stress.

superoxide dismutase 2; oxidative stress; mitochondria; hypoxia

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