Cerebral microvascular responses to endothelins: the role of ETA receptors.
Cerebral microvascular responses to endothelins: the role of ETA receptors.
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脑微血管对内皮素的反应：ETA 受体的作用。
DOI：
10.1016/s0006-8993(09)90024-5
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发表时间：
1994
期刊：
影响因子：
2.9
通讯作者：
Lee,KS
中科院分区：
文献类型：
--
作者：
Sagher,O;Jin,Y;Thai,QA;Fergus,A;Kassell,NF;Lee,KS
内皮素在脑微血管中的调节作用在最近开发的模型系统中进行了研究，该模型系统允许研究正常微环境中的小脑血管。使用大鼠新皮层脑片，结果表明，异肽内皮素-3（ET-3）对脑微血管没有影响，而异肽内皮素-1（ET-1）产生有效的、剂量依赖性的血管收缩。当在用ET-1治疗之前给予最近开发的ETA受体拮抗剂（cyclo-[D-Asp-L-Pro-D-Val-L-Leu-D-Trp]; ETant）时，对ET-1的血管收缩反应以剂量依赖性方式被抑制。当ET-1建立收缩后给予ETant时，对ET-1的收缩反应部分逆转，并且这种作用比预处理范例中所见的弱。这些结果表明，脑微血管对ET-1的收缩反应是由ETA受体介导的。由于内皮素与CNS中血管收缩的病理形式有关，本研究结果还表明内皮素拮抗剂可用于治疗脑缺血。
The regulatory role of endothelins in cerebral microvessels was investigated in a recently developed model system which allows the study of small cerebral vessels in their normal microenvironment. Using brain slices of the rat neocortex, it was shown that the isopeptide endothelin-3 (ET-3) had no effect on cerebral microvessels, while the isopeptide endothelin-1 (ET-1) produced a potent, dose-dependent vasoconstriction. When a recently developed antagonist of ETA receptors (cyclo-[D-Asp-L-Pro-D-Val-L-Leu-D-Trp]; ETant) was administered prior to treatment with ET-1, the vasoconstrictor response to ET-1 was inhibited in a dose-dependent manner. When ETant was administered after the establishment of a constriction by ET-1, the constrictor response to ET-1 was partially reversed, and this effect was weaker than that seen in the pre-treatment paradigm. These findings indicate that constrictor responses to ET-1 in cerebral microvessels are mediated by ETA receptors. Inasmuch as endothelins have been implicated in pathological forms of vasoconstriction in the CNS, the present findings also suggest that endothelin antagonists may be useful in the treatment of cerebral ischemia.