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Vasomotor responses in MnSOD-deficient mice
Jon J Andresen1, Frank M Faraci, Donald D Heistad
1Department of Internal Medicine, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, Iowa 52242, USA.
Abstract:
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.
Insights
Manganese Superoxide Dismutase (MnSOD) deficiency does not alter aortic vasomotor function under normal or oxidative stress conditions. This suggests reduced mitochondrial superoxide may protect nitric oxide bioavailability during stress.
Area of Science:
- Biochemistry
- Physiology
- Cardiovascular Research
Background:
- Manganese Superoxide Dismutase (MnSOD) is essential for mammalian life.
- MnSOD deficient mice exhibit increased susceptibility to oxidative stress.
- Vasomotor function is crucial for regulating blood flow and pressure.
Purpose of the Study:
- To investigate the impact of MnSOD deficiency on aortic vasomotor function.
- To assess responses under normal and induced oxidative stress conditions.
- To explore the role of MnSOD in nitric oxide bioavailability.
Main Methods:
- Comparative analysis of wild-type (WT) and MnSOD(+/-) mouse aortas.
- Assessment of contractile and relaxant responses to various stimuli (serotonin, PGF2alpha, ACh).
- Evaluation of superoxide levels and effects of specific SOD inhibitors (DDC, Tiron) and hypoxia.
Main Results:
- No significant differences in basal vasomotor function or superoxide levels between WT and MnSOD(+/-) aortas.
- Similar impairment of relaxation to ACh and contraction to PGF2alpha by mitochondrial inhibition.
- DDC treatment paradoxically increased contraction and superoxide in WT more than MnSOD(+/-) aortas, with Tiron normalizing responses.
Conclusions:
- Aortic vasomotor function is preserved in MnSOD(+/-) mice under normal and acute oxidative stress.
- Reduced mitochondrial superoxide production in MnSOD deficiency may protect nitric oxide bioavailability.
- Findings suggest compensatory mechanisms in MnSOD-deficient mice regarding vascular function.
