内皮素-3诱导的离体大鼠基底动脉舒张是由内皮ETB型内皮素受体介导的。

Endothelin-3-induced relaxation of isolated rat basilar artery is mediated by an endothelial ETB-type endothelin receptor.

作者信息

Schilling L, Feger G I, Ehrenreich H, Wahl M

机构信息

Department of Physiology, University of Munich, Germany.

出版信息

J Cereb Blood Flow Metab. 1995 Jul;15(4):699-705. doi: 10.1038/jcbfm.1995.86.

DOI:10.1038/jcbfm.1995.86

PMID:7540622

Abstract

The endothelin (ET) receptor mediating relaxation of cerebral arteries was characterized using ring segments obtained from the rat basilar artery. Under resting tension, ET-3 (> 10(-8) M) but not the specific ETB receptor agonist IRL 1620 induced contraction. In ring segments precontracted with 3 x 10(-6) M prostaglandin (PG) F2 alpha, ET-3 (10(-12) - 10(-8) M) and IRL 1620 (10(-14) - 10(-6) M) induced concentration-related relaxation. IRL 1620 was more potent than ET-3, the pD2 (-log10EC50) values being 10.002 +/- 0.751 (mean +/- SD) for IRL 1620 and 8.836 +/- 0.415 for ET-3. Relaxation was abolished after preincubation with the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine (10(-5) M) as well as in segments devoid of a functionally intact endothelium. At a concentration above 10(-8) M, ET-3 resulted in a further increase of PGF2 alpha-induced contraction that was not observed with IRL 1620. The presumably specific ETB receptor antagonist IRL 1038 (10(-7) - 3 x 10(-6) M) diminished or even abolished (3 x 10(-6) M) the relaxation induced by ET-3 or IRL 1620. IRL 1038 did not exert any vasomotor effect by itself, and it did not significantly affect ET-3-induced contraction. These results indicate that in the rat isolated basilar artery, the ET-3-induced relaxation is probably due to activation of an ETB-type receptor located on the endothelial cells and mediated by release of nitric oxide.

摘要

利用从大鼠基底动脉获取的血管环段对介导脑动脉舒张的内皮素（ET）受体进行了特性研究。在静息张力下，ET - 3（>10⁻⁸ M）而非特异性ETB受体激动剂IRL 1620可诱导收缩。在预先用3×10⁻⁶ M前列腺素（PG）F2α预收缩的血管环段中，ET - 3（10⁻¹² - 10⁻⁸ M）和IRL 1620（10⁻¹⁴ - 10⁻⁶ M）可诱导浓度依赖性舒张。IRL 1620比ET - 3更有效，IRL 1620的pD2（-log₁₀EC₅₀）值为10.002±0.751（均值±标准差），ET - 3的pD2值为8.836±0.415。在用一氧化氮（NO）合酶抑制剂NG - 硝基 - L - 精氨酸（10⁻⁵ M）预孵育后以及在缺乏功能完整内皮的血管段中，舒张作用消失。在浓度高于10⁻⁸ M时，ET - 3导致PGF2α诱导的收缩进一步增强，而IRL 1620未观察到这种情况。推测的特异性ETB受体拮抗剂IRL 1038（10⁻⁷ - 3×10⁻⁶ M）可减弱甚至消除（3×10⁻⁶ M）ET - 3或IRL 1620诱导的舒张。IRL 1038自身不产生任何血管运动效应，且对ET - 3诱导的收缩无显著影响。这些结果表明，在大鼠离体基底动脉中，ET - 3诱导的舒张可能是由于位于内皮细胞上的ETB型受体激活并由一氧化氮释放介导。