Alteration of volume-regulated chloride movement in rat cerebrovascular smooth muscle cells during hypertension
Alteration of volume-regulated chloride movement in rat cerebrovascular smooth muscle cells during hypertension
复制标题
高血压期间大鼠脑血管平滑肌细胞容量调节氯运动的改变
DOI：
10.1161/hypertensionaha.106.084657
复制
发表时间：
2007-06-01
期刊：
影响因子：
8.3
通讯作者：
Guan, Yong-Yuan
中科院分区：
文献类型：
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作者：
Shi, Xiao-Lian;Wang, Guan-Lei;Guan, Yong-Yuan
脑血管重构是高血压的一个显著特征，被认为是卒中的主要危险因素。在这一病理生理过程中，脑血管平滑肌细胞受到体积的挑战。我们以前的研究表明，容量调节的氯离子通道可能在血管平滑肌细胞的细胞周期中起关键作用。然而，目前尚不清楚高血压患者的容量调节氯离子运动是否发生改变。因此，我们用6-甲氧基-N-乙基喹啉碘化物荧光探针直接测定了正常大鼠和部分肾动脉缩窄后高血压1~12周大鼠的基底动脉平滑肌细胞内氯离子浓度。等渗液中的[Cl-](I)在各组间无差异。低张灌流后，高血压性脑血管平滑肌细胞[Cl-](I)的降低较假手术对照组更为明显。蛋白酪氨酸激酶抑制剂金雀异黄素抑制低渗诱导的[Cl-](I)还原，而蛋白酪氨酸磷酸酶抑制剂原钒酸钠则增强低渗诱导的[Cl-](I)还原。在2肾2夹高血压组，金雀异黄素对容量调节氯离子运动的[Cl-](I)还原抑制百分率与血压水平呈正相关，而原钒酸钠使[Cl-](I)还原百分率增加。血管紧张素转换酶抑制剂卡托普利的降压治疗完全逆转了高血压大鼠异常的容量调节性氯运动。我们得出结论，在大鼠脑血管平滑肌细胞中，容量调节的氯运动与高血压的严重程度成比例增加。
The cerebrovascular remodeling is a prominent feature of hypertension and considered a major risk factor for stroke. Cerebrovascular smooth muscle cells meet volume challenge during this pathophysiological process. Our previous studies suggest that volume regulated chloride channels may be critical to the cell cycle of vascular smooth muscle cells. However, it is unknown whether the volume-regulated chloride movement is altered in hypertension. Therefore, we directly measured the concentration of intracellular chloride ([Cl-](i)) in rat basilar arterial smooth muscle cells isolated from control rats and rats that were made hypertensive for 1 to 12 weeks after partial renal artery constriction (2-kidney, 2-clip method) using a 6-methoxy-N-ethylquinolinium iodide fluorescence probe. The [Cl-](i) in isotonic solution showed no difference in all of the groups. After hypotonic perfusion, the reduction in [Cl-](i) was more prominent in hypertensive cerebrovascular smooth muscle cells than in sham control cells. Genistein, a protein tyrosine kinase inhibitor, inhibited hypotonic-induced reduction in [Cl-](i), whereas sodium orthovanadate, a protein-tyrosine phosphatase inhibitor, enhanced hypotonic-induced reduction in [Cl-](i) in both groups. The percentage inhibition of reduction in [Cl-](i) by genistein on volume-regulated chloride movement has a positive correlation with blood pressure levels in the 2-kidney, 2-clip hypertensive group, as is the case for the percentage increase of reduction in [Cl-](i) by sodium orthovanadate. Antihypertensive therapy with the angiotensin-converting enzyme inhibitor captopril completely reversed abnormal volume-regulated chloride movement in hypertensive rats. We conclude that volume-regulated chloride movement is augmented in rat cerebrovascular smooth muscle cells in proportion to the severity of hypertension.