High blood pressure upregulates arterial L-type Ca2+ channels -: Is membrane depolarization the signal?
High blood pressure upregulates arterial L-type Ca2+ channels -: Is membrane depolarization the signal?
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DOI：
10.1161/01.res.0000131495.93500.3c
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发表时间：
2004-05-28
影响因子：
20.1
通讯作者：
Rusch, NJ
中科院分区：
文献类型：
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作者：
Pesic, A;Madden, JA;Rusch, NJ
Ca(V)1.2基因家族的长时间钙通道(Ca-L)参与了高血压动脉张力异常的发病机制。增强血管平滑肌细胞(VSMCs)钙-L通道电流的生理刺激尚不清楚。本研究探讨高血压是否触发血管钙-L通道蛋白上调。在左肾(LR)和右肾(RR)动脉的起始处捆绑大鼠主动脉，以选择性地升高RR近端动脉的血压。2天后，与钙-L通道的成孔α(1C)亚单位相对应的Western blotts免疫反应强度在RR动脉是LR动脉的3.25倍。这一发现持续到第28天，与高压下VSMC的钙依赖张力异常和较高的钙电流有关。基于微电极研究表明，与LR动脉相比，RR动脉被去极化，进一步的研究考察了膜去极化是否增加了α(1C)的表达。膜去极化是VSMCs对高血压的固有反应。分离的大鼠肾动脉在低K+(4 mmoL/L)或去极化高K+(30 mmoL/L)的培养液中培养2d。高K+预适应后，α(1C)表达增加5.47倍，钙-L通道电流增强，钙依赖张力增加。这些发现首次提供了高血压上调血管平滑肌细胞钙-L通道α(1C)亚单位的直接证据，并提示膜去极化是参与这种相互作用的潜在信号，可能有助于异常血管张力的发展。
Long-lasting Ca2+ (Ca-L) channels of the Ca(v)1.2 gene family contribute to the pathogenesis of abnormal arterial tone in hypertension. The physiological stimulus that enhances Ca-L channel current in the vascular smooth muscle cells (VSMCs) remains unknown. The present study investigated if high blood pressure triggers an upregulation of vascular Ca-L channel protein. Rat aortae were banded between the origins of the left renal (LR) and right renal (RR) arteries to selectively elevate blood pressure in the proximal RR arteries. After 2 days, the immunoreactivity on Western blots corresponding to the pore-forming alpha(1C) subunit of the Ca-L channel was increased 3.25-fold in RR compared with LR arteries. This finding persisted at 28 days and was associated with abnormal Ca2+-dependent tone and higher CaL currents in the VSMCs exposed to high pressure. Based on microelectrode studies indicating that RR arteries were depolarized compared with LR arteries, further studies examined if membrane depolarization, an inherent response of VSMCs to high blood pressure, increased alpha(1C) expression. Isolated rat renal arteries were cultured for 2 days in low K+ (4 mmol/L) or depolarizing high K+ (30 mmol/L) media. Arteries preconditioned in high K+ showed a 5.47-fold increase in alpha(1C) expression, enhanced Ca-L channel current, and elevated Ca2+-dependent tone. These findings provide the first direct evidence that high blood pressure upregulates the Ca-L channel alpha(1C) subunit in VSMCs in vivo and suggest that membrane depolarization is a potential signal involved in this interaction that may contribute to the development of abnormal vascular tone.