Journal
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
Volume 287, Issue 3, Pages H1141-H1148Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.01215.2003
Keywords
superoxide dismutase 2; oxidative stress; mitochondria; hypoxia
Funding
- NHLBI NIH HHS [HL-16066, HL-38901, HL-62984] Funding Source: Medline
- NIA NIH HHS [AG-00214] Funding Source: Medline
- NINDS NIH HHS [NS-42502, NS-24621] Funding Source: Medline
Ask authors/readers for more resources
MnSOD is the only mammalian isoform of SOD that is necessary for life. MnSOD-/- mice die soon after birth, and Mn-SOD+/- 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 F-2alpha (PGF(2alpha)), relaxation to ACh, and superoxide levels were similar in aortas of WT and MnSOD+/- mice. The mitochondrial inhibitor antimycin A reduced contraction to PGF(2alpha) 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 PGF(2alpha) 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available