Aldosterone regulates the Na-K-2Cl cotransporter in vascular smooth muscle
Aldosterone regulates the Na-K-2Cl cotransporter in vascular smooth muscle
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DOI：
10.1161/01.hyp.0000066128.04083.ca
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发表时间：
2003-05-01
期刊：
影响因子：
8.3
通讯作者：
O'Neill, WC
中科院分区：
文献类型：
--
作者：
Jiang, GR;Cobbs, S;O'Neill, WC
醛固酮增加了血管平滑肌的阳离子转运和收缩能力，但具体涉及的转运体以及它是如何与平滑肌张力联系在一起的尚不清楚。由于Na-K-2Cl共转运体(NKCC1)参与血管平滑肌收缩，并受血管活性物质的调节，因此我们试图确定该转运体是否是大鼠主动脉中的醛固酮靶标。用醛固酮处理肾上腺切除大鼠7天后，用布美他尼敏感的Rb-86(+)外排检测，NKCC1活性增加了63%。用醛固酮处理正常主动脉3天和7天后，NKCC1活性分别增加29%和47%。醛固酮对Rb-86(+)外排无急性影响。NKCC1的兴奋可被盐皮质激素受体拮抗剂螺内酯阻断，但不能被糖皮质激素受体拮抗剂RU38486阻断。实时定量聚合酶链式反应显示，醛固酮不能增强苯肾上腺素对NKCC1的刺激作用，也不能增加NKCC1mRNA的表达。我们的结论是，醛固酮通过经典的盐皮质激素受体而不是通过改变NKCC1mRNA的丰度来调节血管平滑肌中的Na-K-2Cl共转运体。这可能解释了先前在盐皮质激素治疗的动物中观察到的血管平滑肌中Na+、K+和Cl-流量的增加，并可能有助于增加血管张力。
Aldosterone increases cation transport and contractility of vascular smooth muscle, but the specific transporter involved and how it is linked to smooth muscle tone is unknown. Because the Na-K-2Cl cotransporter (NKCC1) contributes to vascular smooth muscle contraction and is regulated by vasoactive compounds, we sought to determine whether this transporter is a target of aldosterone in rat aorta. Treatment of adrenalectomized rats with aldosterone for 7 days resulted in a 63% increase in NKCC1 activity as measured by bumetanide-sensitive efflux of Rb-86(+). Treatment of normal aortas in culture with aldosterone for 3 and 7 days resulted in 29% and 47% increases in NKCC1 activity, respectively. Aldosterone had no acute effect on Rb-86(+) efflux. Stimulation of NKCC1 was blocked by spironolactone, a mineralocorticoid receptor antagonist, but not by RU38486, a glucocorticoid receptor antagonist. Aldosterone did not augment the stimulation of NKCC1 by phenylephrine and did not increase NKCC1 mRNA as determined by real-time polymerase chain reaction. We conclude that aldosterone regulates the Na-K-2Cl cotransporter in vascular smooth muscle through classic mineralocorticoid receptors but not through changes in the abundance of NKCC1 mRNA. This could account for the increase in Na+, K+, and Cl- fluxes previously observed in vascular smooth muscle from mineralocorticoid-treated animals and may contribute to increased vascular tone.