Estrogen modulation of eNOS activity and its association with caveolin-3 and calmodulin in rat hearts.
Estrogen modulation of eNOS activity and its association with caveolin-3 and calmodulin in rat hearts.
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DOI：
10.1152/ajpheart.00772.2001
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发表时间：
2002-06
期刊：
影响因子：
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通讯作者：
Xu Wang;A. Abdel‐Rahman
中科院分区：
文献类型：
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作者：
Xu Wang;A. Abdel‐Rahman
以往的研究表明，雌激素调节内皮型一氧化氮合酶（eNOS）可能会对心脏病提供保护。在这里，我们证明了压力反射介导的心动过缓和心脏NOS活性在卵巢切除（OVX）大鼠与对照组相比，减少之间的关联。后者至少部分是由于心脏eNOS蛋白的减少。eNOS衍生的NO及其生物学效应由eNOS蛋白的水平和eNOS催化活性决定;后者部分通过与抑制蛋白（小窝蛋白）和刺激蛋白（钙调蛋白）的动态相互作用来调节。eNOS免疫沉淀与小窝蛋白-3和钙调蛋白的协会进行了检查。在卵巢切除大鼠中，Caveolin-3和钙调素与eNOS的结合分别增加和减少。17 β-雌二醇替代使压力感受性反射介导的心动过缓反应与eNOS活性、eNOS表达以及eNOS与小窝蛋白-3和钙调蛋白的结合沿着恢复至正常水平。我们的研究结果可能有助于阐明雌激素对压力感受性反射激活的心脏反应有利影响的分子机制。
Previous studies have shown that estrogen modulation of endothelial nitric oxide (NO) synthase (eNOS) may confer protection against heart disease. Here, we demonstrate an association between reductions in baroreflex-mediated bradycardia and in cardiac NOS activity in ovariectomized (Ovx) rats compared with controls. The latter resulted, at least in part, from a reduction in cardiac eNOS protein. eNOS-derived NO and its biological effects are determined by the levels of eNOS protein and by eNOS catalytic activity; the latter is regulated partly through the dynamic interaction with an inhibitory protein (caveolin) and a stimulatory protein (calmodulin). The association of eNOS immunoprecipitated with caveolin-3 and calmodulin was examined. Caveolin-3 and calmodulin binding with eNOS was increased and decreased, respectively, in Ovx rats. 17 beta-Estradiol replacement restored, to within normal levels, the baroreflex-mediated bradycardic responses along with eNOS activity, eNOS expression, and the association of eNOS with caveolin-3 and calmodulin. Our findings may help to elucidate the molecular mechanism underlying the favorable effects of estrogen on cardiac responses to baroreflex activation.