Feng Ming-Guo, Navar L Gabriel
Department of Physiology, Hypertension and Renal Center of Excellence, Tulane University School of Medicine, New Orleans, La. 70112, USA.
Am J Nephrol. 2004 Nov-Dec;24(6):641-8. doi: 10.1159/000082946. Epub 2004 Dec 23.
BACKGROUND/AIMS: Previous studies have shown that L-type Ca2+ channel (LCC) blockers prevent the afferent arteriolar (AA) vasoconstriction elicited by angiotensin II (Ang II), but do not influence its vasoconstrictor effect on efferent arterioles (EA). The present study tested the hypothesis that Ang II-mediated constriction of AA and EA involves T-type Ca2+ channel (TCC) activation, which may mediate Ca2+ entry responsible for Ang II-induced EA and possibly AA constriction.
Video-microscopic measurements of vascular dimensions were performed on isolated blood-perfused juxtamedullary nephrons from Sprague-Dawley rats. Single AA or EA were visualized and superfused with solutions containing Ang II alone or with a TCC blocker, pimozide, or a LCC blocker, diltiazem.
Pimozide at 10 micromol/l significantly dilated EA (19.7 +/- 1.4%) as well as AA (24.8 +/- 3.6%). In response to superfusion with Ang II at concentrations of 0.1, 1.0 and 10.0 nmol/l, AA diameter decreased significantly by 15.2 +/- 1.7, 23.3 +/- 3.2 and 36.1 +/- 3.4% and EA diameter also decreased significantly by 11.9 +/- 1.7, 19.6 +/- 2.8 and 31.0 +/- 2.6%, respectively. Pimozide (10 micromol/l) markedly blunted AA (4.6 +/- 1.2, 7.5 +/- 0.6 and 7.9 +/- 1.2%) and EA (2.2 +/- 0.6, 5.4 +/- 1.5 and 7.7 +/- 1.3%) diameter responses to Ang II. Diltiazem (10 micromol/l) significantly dilated AA (26.8 +/- 2.2%), and prevented Ang II-mediated constriction of AA. In contrast, diltiazem did not dilate EA (3.3 +/- 0.6%) and failed to inhibit the Ang II-induced EA vasoconstriction; however, the vasoconstriction was reversed by the subsequent addition of pimozide (5 micromol/l).
This study provides further functional evidence for TCC channels in the regulation of AA and EA indicating that Ang II-mediated arteriolar constriction may involve activation of TCC in both AA and EA. TCC may play an important role in mediating Ca2+ entry responsible for Ang-induced EA and AA constriction. The role of TCC in mediating Ang II-constrictor actions on EA may be of particular significance because LCC are not normally functional in these vessels.
背景/目的：以往研究表明，L型钙通道（LCC）阻滞剂可阻止血管紧张素II（Ang II）引起的入球小动脉（AA）血管收缩，但不影响其对出球小动脉（EA）的血管收缩作用。本研究检验了以下假设：Ang II介导的AA和EA收缩涉及T型钙通道（TCC）激活，这可能介导负责Ang II诱导的EA以及可能的AA收缩的钙内流。
对来自Sprague-Dawley大鼠的分离的血液灌注近髓肾单位进行血管尺寸的视频显微镜测量。观察单个AA或EA，并分别用仅含Ang II的溶液或含TCC阻滞剂匹莫齐特或LCC阻滞剂地尔硫卓的溶液进行灌流。
10 μmol/l的匹莫齐特可使EA（19.7±1.4%）和AA（24.8±3.6%）显著扩张。用浓度为0.1、1.0和10.0 nmol/l的Ang II灌流时，AA直径分别显著减小15.2±1.7%、23.3±3.2%和36.1±3.4%，EA直径也分别显著减小11.9±1.7%、19.6±2.8%和31.0±2.6%。10 μmol/l的匹莫齐特显著减弱了AA（4.6±1.2%、7.5±0.6%和7.9±1.2%）和EA（2.2±0.6%、5.4±1.5%和7.7±1.3%）对Ang II的直径反应。10 μmol/l的地尔硫卓使AA显著扩张（26.8±2.2%），并阻止了Ang II介导的AA收缩。相比之下，地尔硫卓未使EA扩张（3.3±0.6%），也未能抑制Ang II诱导的EA血管收缩；然而，随后加入5 μmol/l的匹莫齐特可使血管收缩逆转。
本研究为TCC通道在AA和EA调节中的作用提供了进一步的功能证据，表明Ang II介导的小动脉收缩可能涉及AA和EA中TCC的激活。TCC可能在介导负责Ang诱导的EA和AA收缩的钙内流中起重要作用。TCC在介导Ang II对EA的收缩作用中的作用可能尤为重要，因为LCC在这些血管中通常不起作用。
