Heart mitochondrial nitric oxide synthase is upregulated in male rats exposed to high altitude (4,340 m)
Heart mitochondrial nitric oxide synthase is upregulated in male rats exposed to high altitude (4,340 m)
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DOI：
10.1152/ajpheart.00812.2004
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发表时间：
2005-06-01
影响因子：
4.8
通讯作者：
Boveris, A
中科院分区：
文献类型：
--
作者：
Gonzales, GF;Chung, FA;Boveris, A
雄性大鼠暴露在高海拔（4，340米）21天后，体重增长停止，红细胞比容和睾酮水平升高。高海拔显著（58%）增加心脏线粒体一氧化氮（NO）合酶（mtNOS）活性，而心脏细胞质内皮NOS（eNOS）和肝脏mtNOS不受影响。Western印迹分析发现，心脏线粒体只与抗诱导型一氧化氮合酶（iNOS）抗体反应，而postmitochondrial馏分与抗iNOS和抗eNOS抗体反应。在体外测量的NOS活性允许估计心肌细胞产生NO的能力，该值从57%（海平面）增加到79 nmol NO.min（-1）.g心脏（-1）（4，340 m）。线粒体NOS对细胞NO总生成的贡献从62%（海平面）增加到71%（4340 m）。心肌线粒体一氧化氮合酶活性与红细胞压积呈线性关系，与雌二醇和睾酮呈二次相关。多因素分析显示，高原暴露与红细胞压积和心脏mtNOS活性呈线性相关，而睾酮/雌二醇比值和心脏重量与mtNOS活性不呈线性相关。我们的结论是，高海拔引发的生理适应性反应，上调心脏线粒体NOS活性，并与血清睾酮和雌二醇水平的相反的方式。
Male rats exposed for 21 days to high altitude (4,340 m) responded with arrest of weight gain and increased hematocrit and testosterone levels. High altitude significantly (58%) increased heart mitochondrial nitric oxide (NO) synthase (mtNOS) activity, whereas heart cytosolic endothelial NOS (eNOS) and liver mtNOS were not affected. Western blot analysis found heart mitochondria reacting only with anti-inducible NOS (iNOS) antibodies, whereas the postmitochondrial fraction reacted with anti-iNOS and anti-eNOS antibodies. In vitro-measured NOS activities allowed the estimation of cardiomyocyte capacity for NO production, a value that increased from 57% (sea level) to 79 nmol NO.min(-1).g heart(-1) (4,340 m). The contribution of mtNOS to total cell NO production increased from 62% (sea level) to 71% (4340 m). Heart mtNOS activity showed a linear relationship with hematocrit and a biphasic quadratic association with estradiol and testosterone. Multivariate analysis showed that exposure to high altitude linearly associates with hematocrit and heart mtNOS activity, and that testosterone-to-estradiol ratio and heart weight were not linearly associated with mtNOS activity. We conclude that high altitude triggers a physiological adaptive response that upregulates heart mtNOS activity and is associated in an opposed manner with the serum levels of testosterone and estradiol.