Vasomotor responses in MnSOD-deficient mice

被引:26
作者
Andresen, JJ
Faraci, FM
Heistad, DD
机构
[1] Univ Iowa, Roy J & Lucille A Carver Coll Med, Dept Internal Med, Iowa City, IA 52242 USA
[2] Univ Iowa, Roy J & Lucille A Carver Coll Med, Dept Pharmacol, Iowa City, IA 52242 USA
[3] Vet Adm Med Ctr, Iowa City, IA 52242 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 2004年 / 287卷 / 03期
关键词
superoxide dismutase 2; oxidative stress; mitochondria; hypoxia;
D O I
10.1152/ajpheart.01215.2003
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:H1141 / H1148
页数:8
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