Vasomotor responses in MnSOD-deficient mice
Vasomotor responses in MnSOD-deficient mice
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DOI：
10.1152/ajpheart.01215.2003
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发表时间：
2004-09-01
影响因子：
4.8
通讯作者：
Heistad, DD
中科院分区：
文献类型：
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作者：
Andresen, JJ;Faraci, FM;Heistad, DD
MnSOD是唯一的哺乳动物SOD的同种型是必需的生活。MnSOD-/-小鼠在出生后不久死亡，Mn-SOD+/-小鼠比野生型（WT）小鼠更容易受到氧化应激的影响。在这项研究中，我们研究了MnSOD-/-小鼠在正常条件下和氧化应激过程中的血管功能反应。在正常条件下，WT和MnSOD+/-小鼠的睾丸对5-羟色胺（5-HT）和前列腺素F-2 α（PGF（2 α））的收缩，对乙酰胆碱的舒张，以及超氧化物水平相似。在WT和MnSOD+/-小鼠的子宫内膜中，线粒体抑制剂抗霉素A减少了对PGF（2 α）的收缩，并损害了对ACh的舒张。Cu/ZnSOD和细胞外SOD抑制剂二乙基二硫代氨基甲酸酯（DDC）矛盾地增强WT小鼠睾丸对5-HT和超氧阴离子的收缩作用。DDC损害ACh的松弛和降低总SOD活性相似，在两种基因型的factas。Tiron是一种超氧化物清除剂，在经DDC处理的WT和MnSOD+/-小鼠睾丸中使5-HT收缩、ACh松弛和超氧化物水平正常化。缺氧，据报道，增加超氧化物，减少收缩5-HT和PGF（2 α）类似的WT和MnSOD+/-小鼠的睾丸。两种基因型对急性缺氧的血管反应相似。总之，在正常条件下和急性氧化应激期间，WT和MnSOD+/-小鼠的血管功能相似。我们推测，减少线粒体超氧化物的产生可能会保持氧化应激过程中一氧化氮的生物利用度。
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.