Vasomotor responses in MnSOD-deficient mice.
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 F2alpha (PGF2alpha), relaxation to ACh, and superoxide levels were similar in aortas of WT and MnSOD(+/-) mice. The mitochondrial inhibitor antimycin A reduced contraction to PGF2alpha 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 PGF2alpha 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.
Department of Internal Medicine, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, Iowa 52242, USA.
Jon J
JJ
Andresen
Frank M
FM
Faraci
Donald D
DD
Heistad
D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D002614:Chelating Agents / Q000494:pharmacology; D004050:Ditiocarb / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress; D013482:Superoxide Dismutase / Q000172:deficiency*; D014666:Vasomotor System / Q000502:physiology* / Q000503:physiopathology
D002614:Chelating Agents; D000968:Antimycin A; D004050:Ditiocarb; D013482:Superoxide Dismutase