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首页> 外文期刊>American Journal of Physiology >Upregulation of Na+ and Ca2+ transporters in arterial smooth muscle from ouabain-induced hypertensive rats.
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Upregulation of Na+ and Ca2+ transporters in arterial smooth muscle from ouabain-induced hypertensive rats.

机译：哇巴因诱导的高血压大鼠动脉平滑肌中Na +和Ca2 +转运蛋白的上调。

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摘要

Prolonged ouabain administration (25 microg kg(-1) day(-1) for 5 wk) induces ouabain hypertension ouabain elevates blood pressure are unknown. Here, we compared Ca(2+) signaling in mesenteric artery smooth muscle cells (ASMCs) from normotensive (NT) and OH rats. Resting cytosolic free Ca(2+) concentration ([Ca(2+)](cyt); measured with fura-2) and phenylephrine-induced Ca(2+) transients were augmented in freshly dissociated OH ASMCs. Immunoblots revealed that the expression of the ouabain-sensitive alpha(2)-subunit of Na(+) pumps, but not the predominant, ouabain-resistant alpha(1)-subunit, was increased (2.5-fold vs. NT ASMCs) as was Na(+)/Ca(2+) exchanger-1 (NCX1; 6-fold vs. NT) in OH arteries. Ca(2+) entry, activated by sarcoplasmic reticulum (SR) Ca(2+) store depletion with cyclopiazonic acid (SR Ca(2+)-ATPase inhibitor) or caffeine, was augmented in OH ASMCs. This reflected an augmented expression of 2.5-fold in OH ASMCs of C-type transient receptor potential TRPC1, an essential component of store-operated channels (SOCs); two other components of some SOCs were not expressed (TRPC4) or were not upregulated (TRPC5). Ba(2+) entry activated by the diacylglycerol analog 1-oleoyl-2-acetyl-sn-glycerol [a measure of receptor-operated channel (ROC) activity] was much greater in OH than NT ASMCs. This correlated with a sixfold upregulation of TRPC6 protein, a ROC family member. Importantly, in primary cultured mesenteric ASMCs from normal rats, 72-h treatment with 100 nM ouabain significantly augmented NCX1 and TRPC6 protein expression and increased resting [Ca(2+)](cyt) and ROC activity. SOC activity was also increased. Silencer RNA knockdown of NCX1 markedly downregulated TRPC6 and eliminated the ouabain-induced augmentation; silencer RNA knockdown of TRPC6 did not affect NCX1 expression but greatly attenuated its upregulation by ouabain. Clearly, NCX1 and TRPC6 expression are interrelated. Thus, prolonged ouabain treatment upregulates the Na(+) pump alpha(2)-subunit-NCX1-TRPC6 (ROC) Ca(2+) signaling pathway in arterial myocytes in vitro as well as in vivo. This may explain the augmented myogenic responses and enhanced phenylephrine-induced vasoconstriction in OH arteries (83) as well as the high blood pressure in OH rats.
机译：长期服用哇巴因（25微克kg（-1）天（-1）连续5周）会诱发哇巴因高血压哇巴因会升高血压是未知的。在这里，我们比较了来自正常血压（NT）和OH大鼠的肠系膜动脉平滑肌细胞（ASMC）中的Ca（2+）信号传导。在新鲜离解的OH ASMC中增加了静息的胞质游离Ca（2+）浓度（[Ca（2 +）]（cyt）;用fura-2测量）和去氧肾上腺素诱导的Ca（2+）瞬变。免疫印迹显示，Na（+）泵对哇巴因敏感的α（2）-亚基的表达增加了，但对耐哇巴因的主要α（1）-亚基却没有增加（相对于NT ASMC为2.5倍）在OH动脉中是Na（+）/ Ca（2+）交换子-1（NCX1;对NT为6倍）。 Ca（2+）进入，由肌质网（SR）Ca（2+）存储耗尽与环吡嗪酸（SR Ca（2 +）-ATPase抑制剂）或咖啡因，在OH ASMCs中增加。这反映出在C型瞬时受体电位TRPC1（存储操作通道（SOC）的重要组成部分）的OH ASMC中表达增加了2.5倍。一些SOC的其他两个组件未表达（TRPC4）或未上调（TRPC5）。 Ba（2+）进入由二酰基甘油类似物1-油酰基-2-乙酰基-sn-甘油[衡量的受体操作通道（ROC）活性的一种措施]在OH中比NT ASMCs大得多。这与ROC家族成员TRPC6蛋白的六倍上调相关。重要的是，在正常大鼠的原代培养肠系膜ASMC中，用100 nM哇巴因处理72小时可显着增加NCX1和TRPC6蛋白的表达，并增加静息[Ca（2 +）]（cyt）和ROC活性。 SOC活性也增加了。 NCX1的沉默子RNA抑制显着下调了TRPC6并消除了哇巴因诱导的扩增。 TRPC6的沉默子RNA敲低并不影响NCX1表达，但大大减弱了哇巴因对其的上调。显然，NCX1和TRPC6的表达是相互关联的。因此，延长的哇巴因治疗在体内和体外都在动脉心肌细胞中上调了Na（+）泵alpha（2）-亚基-NCX1-TRPC6（ROC）Ca（2+）信号通路。这可能解释了OH动脉中肌源性反应的增强和苯肾上腺素诱导的血管收缩的增强（83）以及OH大鼠中的高血压。

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