内皮素-1未参与血管紧张素II诱导的离体大鼠尾动脉收缩。

Lack of involvement of endothelin-1 in angiotensin II-induced contraction of the isolated rat tail artery.

作者信息

Jiang Y, Triggle C R

机构信息

Department of Pharmacology & Therapeutics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada T2N 4N1.

出版信息

Br J Pharmacol. 2000 Nov;131(6):1055-64. doi: 10.1038/sj.bjp.0703674.

DOI:10.1038/sj.bjp.0703674

PMID:11082111

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1572432/

Abstract

The contribution of endothelin-1 (ET-1) to angiotensin II (Ang II)-mediated contraction of the isolated rat tail artery was assessed with measurements of tension, and cytosolic calcium (Ca(2+)). The distribution of the AT(1) receptor was studied with RT - PCR and immunohistochemistry. 2. Ang II induced an endothelium-independent contraction (pEC(50) 7.95+/-0.06 and E(max): 0.46 g+/-0.05 with endothelium vs 7.81+/-0.02 and 0.41 g+/-0.07 without endothelium; P>0.05). Ang II (0.003 - 0.3 microM)-induced a non-sustained contraction of endothelium-intact preparations which was not antagonized by BQ-123 (1 microM), but was inhibited by losartan (10 nM). In addition, the maximal contraction induced by ET-1 (0.1 microM) could be further increased by the addition of 0.1 microM Ang II. 3. Ang II (0.001 - 0.3 microM) elevated Ca(2+) in single vascular smooth muscle cells (VSMCs) in a dose-dependent manner (pEC(50) 9.12+/-0.26) and the Ang II-induced increases in Ca(2+) were not affected by a Ca(2+)-free solution, but were abolished by pretreatment with caffeine (5 mM). Ang II did not increase Ca(2+) in endothelial cells. ET-1 (0.1 microM) increased Ca(2+) in single VSMCs in a normal Ca(2+) containing physiological saline solution (PSS), but not in a Ca(2+)-free solution. 4. Ang II-induced contraction was insensitive to inhibition by nifedipine (0.1 microM), an antagonist of L-type voltage-gated Ca(2+) channels, and SK&F96365 (10 microM), which blocks non-selective cation channels, whereas that to ET-1 was inhibited by SK&F69365. 5. RT - PCR data indicate the expression of AT(1A) and AT(1B) on both VSMCs and endothelial cells, but immunohistochemical evidence illustrates that the AT(1) is located primarily on VSMCs. 6. These results indicate that endothelium-derived ET-1 is not involved in the Ang II-mediated vasoconstriction of the rat tail artery and that Ang II- and ET-1-mediated VSM contractions utilize distinct pathways.

摘要

通过张力测量和胞质钙（Ca(2+)）测量，评估内皮素-1（ET-1）对血管紧张素II（Ang II）介导的离体大鼠尾动脉收缩的作用。采用逆转录-聚合酶链反应（RT-PCR）和免疫组织化学研究AT(1)受体的分布。2. Ang II诱导非内皮依赖性收缩（有内皮时pEC(50) 7.95±0.06，E(max)：0.46 g±0.05；无内皮时7.81±0.02和0.41 g±0.07；P>0.05）。Ang II（0.003 - 0.3 microM）诱导内皮完整制剂的非持续性收缩，该收缩不被BQ-123（1 microM）拮抗，但被氯沙坦（10 nM）抑制。此外，添加0.1 microM Ang II可使ET-1（0.1 microM）诱导的最大收缩进一步增强。3. Ang II（0.001 - 0.3 microM）以剂量依赖性方式升高单个血管平滑肌细胞（VSMC）中的Ca(2+)（pEC(50) 9.12±0.26），Ang II诱导的Ca(2+)升高不受无钙溶液影响，但被咖啡因（5 mM）预处理消除。Ang II未增加内皮细胞中的Ca(2+)。ET-1（0.1 microM）在含正常钙的生理盐溶液（PSS）中增加单个VSMC中的Ca(2+)，但在无钙溶液中不增加。4. Ang II诱导的收缩对L型电压门控钙通道拮抗剂硝苯地平（0.1 microM）和阻断非选择性阳离子通道的SK&F96365（10 microM）的抑制不敏感，而对ET-1诱导的收缩被SK&F69365抑制。5. RT-PCR数据表明VSMC和内皮细胞上均有AT(1A)和AT(1B)表达，但免疫组织化学证据显示AT(1)主要位于VSMC上。6. 这些结果表明，内皮源性ET-1不参与Ang II介导的大鼠尾动脉血管收缩，且Ang II和ET-1介导的VSMC收缩利用不同途径。