L-type calcium channels in the renal microcirculatory response to endothelin.
L-type calcium channels in the renal microcirculatory response to endothelin.
复制标题
DOI：
10.1152/ajprenal.00315.2004
复制
发表时间：
2005-04
期刊：
影响因子：
--
通讯作者：
D. Pollock;John M Jenkins;A. Cook;J. Imig;E. Inscho
中科院分区：
文献类型：
--
作者：
D. Pollock;John M Jenkins;A. Cook;J. Imig;E. Inscho
肾循环中内皮素（ET）-1介导的血管收缩的信号通路尚未阐明，但似乎在ET（A）和ET（B）受体之间存在差异。本研究旨在探讨L型钙通道在内皮素1（ET-1）和内皮素（B）受体激动剂Sarafotoxin 6c（S6 c）缩血管反应中的作用。在麻醉大鼠中，用超声流量探头测量肾血流量（RBF），并将微导管插入肾动脉用于药物输注。所有大鼠均给予溶剂（0.9%NaCl）或三次连续推注（1，10和100 pmol）的ET-1或S6 c，间隔30分钟（每组n = 6）。ET-1和S6 c使RBF呈剂量依赖性降低。Ca（2+）通道阻滞剂硝苯地平（1.5 μ g）仅在最高剂量的ET-1和S6 c下显著减弱RBF反应。在离体血灌流的肾上腺髓质肾单位标本中，用地尔硫卓阻断Ca（2+）通道对ET-1诱导的传入小动脉直径的减小只有很小的抑制作用，仅在最低浓度的ET-1时。在肾小球前血管平滑肌细胞中，ET-1产生典型的双相Ca（2+）反应，而S6 c对胞浆Ca（2+）无影响。此外，Ca（2+）通道阻断剂（地尔硫卓或Ni（2+））对ET-1产生的胞浆Ca（2+）的峰值或持续增加没有影响。这些结果支持了L型Ca（2+）通道在肾微循环对ET-1的收缩反应中仅起次要作用的假设。
The signaling pathways of endothelin (ET)-1-mediated vasoconstriction in the renal circulation have not been elucidated but appear to be distinct between ET(A) and ET(B) receptors. The purpose of this study was to determine the role of L-type Ca(2+) channels in the vasoconstrictor response to ET-1 and the ET(B) receptor agonist sarafotoxin 6c (S6c) in the rat kidney. Renal blood flow (RBF) was measured with an ultrasonic flow probe in anesthetized rats, and a microcatheter was inserted into the renal artery for drug infusion. All rats were given vehicle (0.9% NaCl) or three successive bolus injections (1, 10, and 100 pmol) of ET-1 or S6c at 30-min intervals (n = 6 in each group). ET-1 and S6c produced dose-dependent decreases in RBF. The Ca(2+) channel blocker nifedipine (1.5 mug) significantly attenuated the RBF response only at the highest doses of ET-1 and S6c. In the isolated blood-perfused juxtamedullary nephron preparation, Ca(2+) channel blockade with diltiazem had a very small inhibitory effect on ET-1-induced decreases in afferent arteriolar diameter only at the lowest concentrations of ET-1. In vascular smooth muscle cells isolated from preglomerular vessels, ET-1 produced a typical biphasic Ca(2+) response, whereas S6c had no effect on cytosolic Ca(2+). Furthermore, Ca(2+) channel blockade (diltiazem or Ni(2+)) had no effect on the peak or sustained increase in cytosolic Ca(2+) produced by ET-1. These results support the hypothesis that L-type Ca(2+) channels play only a minor role in the constrictor responses to ET-1 in the renal microcirculation.