Presence of contractile endothelin-A and dilatory endothelin-B receptors in human cerebral arteries
Presence of contractile endothelin-A and dilatory endothelin-B receptors in human cerebral arteries
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DOI：
10.1097/00006123-199702000-00023
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发表时间：
1997-02-01
期刊：
影响因子：
4.8
通讯作者：
Edvinsson, L
中科院分区：
文献类型：
--
作者：
Nilsson, T;Cantera, L;Edvinsson, L
目的：本研究的目的是阐明负责内皮素诱导的人脑动脉血管舒缩反应的内皮素受体亚型。方法：将带有内皮的人脑动脉固定在体外组织浴中，观察血管对内皮素-1（ET-1）和sarafotoxin 6c（一种选择性ET（B）激动剂）的反应 在存在或不存在内皮素阻滞剂、波生坦 (Ro 47-0203)（一种新型非肽 ET(A) 和 ET(B) 受体拮抗剂）和 FR139317（一种选择性 ET(A) 受体拮抗剂）的情况下进行了研究。通过逆转录聚合酶链式反应，研究了具有完整内皮的人脑动脉和内皮剥脱的脑动脉中编码人ET(A)和ET(B)受体的信使核糖核酸的存在。结果：ET-1诱导人脑动脉的浓度依赖性收缩； pEC(50) 值为 9.4 +/- 0.2。波生坦和 FR139317 均显着拮抗血管收缩作用。 pA(2) 值分别为7.2 +/- 0.4 和7.4 +/- 0.4。 Sarafotoxin 6c 未能引起人脑动脉收缩。然而，在预收缩的血管中，sarafotoxin 6c 诱导的扩张被波生坦 (10 mu mol/L) 显着抑制，导致 pA(2) 值为 6.0 +/- 0.2。此外，在有内皮和无内皮的人脑动脉中均检测到编码人 ET(A) 和 ET(B) 受体的信使核糖核酸。结论：ET-1 诱导的人脑动脉血管收缩主要由 ET(A) 受体介导，而 sarafotoxin 6c 诱导的血管舒张似乎是通过 ET(B) 受体。
OBJECTIVE: The aim of the present study was to elucidate the endothelin receptor subtypes responsible for the endothelin-induced vasomotor responses of human cerebral arteries.METHODS: Human cerebral arteries with endothelium were mounted in in vitro tissue baths, and the vascular responses to endothelin-1 (ET-1) and sarafotoxin 6c (a selective ET(B) agonist) were studied in the presence or absence of endothelin blockers, bosentan (Ro 47-0203), a novel nonpeptide ET(A) and ET(B) receptor antagonist, and FR139317, a selective ET(A) receptor antagonist. The presence of messenger ribonucleic acid encoding the human ET(A) and ET(B) receptors in human cerebral arteries with intact endothelium and in segments denuded of endothelium was studied by the use of reverse transcriptase-polymerase chain reaction.RESULTS: ET-1 induced concentration-dependent contraction of human cerebral arteries; the pEC(50) value was 9.4 +/- 0.2. The vasoconstriction was significantly antagonized both by bosentan and by FR139317. The pA(2) values were 7.2 +/- 0.4 and 7.4 +/- 0.4, respectively. Sarafotoxin 6c failed to cause contraction of human cerebral arteries. In precontracted vessels, however, sarafotoxin 6c induced dilatation that was significantly inhibited by bosentan (10 mu mol/L), resulting in a pA(2) value of 6.0 +/- 0.2. Furthermore, messenger ribonucleic acid encoding the human ET(A) and ET(B) receptors was detected in human cerebral arteries both with and without endothelium.CONCLUSION: The ET-1-induced vasoconstriction of human cerebral arteries is primarily mediated by the ET(A) receptor, whereas the sarafotoxin 6c-induced vasodilatation seems to be mediated via the ET(B) receptor.