Clement M G, Albertini M
Institute of Veterinary Physiology and Biochemistry, University of Milan, Italy.
Prostaglandins Leukot Essent Fatty Acids. 1996 Oct;55(4):279-85. doi: 10.1016/s0952-3278(96)90009-5.
The vascular effects of endothelin-1 (ET-1) and the release of prostacyclin and nitric oxide (NO) evoked by this peptide were analyzed in anesthetized, mechanically ventilated pigs. ET-1 induced biphasic responses in both the pulmonary and systemic vascular beds characterized by a transient hypotension followed by a long-lasting hypertension. To evaluate the involvement of prostacyclin and NO in the ET-1-dependent vascular response, we used indomethacin to block cyclooxygenase and NG-nitro-L-arginine methyl ester (L-NAME) to block NO synthase. The results show that the systemic hypotensive response to ET-1 is mediated by the release of prostanoids and NO, but these are not responsible for the pulmonary hypotension. Indomethacin reduced the hypertensive effect of ET-1, showing that this peptide can also activate release of vasoconstrictor cyclooxygenase metabolites. When L-NAME was administered after indomethacin, the pulmonary vasoconstrictor activity of ET-1 was counterbalanced by NO. By contrast, in pigs pretreated with indomethacin plus L-NAME ET-1 caused transient systemic vasoconstriction, followed by progressive reduction of vascular tone, probably because of release of vasodilator agents other than prostanoids or NO.
在麻醉、机械通气的猪身上分析了内皮素 -1（ET -1）的血管效应以及该肽引发的前列环素和一氧化氮（NO）释放。ET -1在肺血管床和体循环血管床均诱导出双相反应，其特征为短暂的低血压，随后是持久的高血压。为评估前列环素和NO在ET -1依赖性血管反应中的作用，我们使用吲哚美辛阻断环氧化酶，并用NG -硝基 -L -精氨酸甲酯（L - NAME）阻断NO合酶。结果表明，ET -1引起的全身低血压反应由前列腺素和NO的释放介导，但它们并非肺低血压的原因。吲哚美辛降低了ET -1的高血压效应，表明该肽还可激活血管收缩性环氧化酶代谢产物的释放。当在吲哚美辛之后给予L - NAME时，ET -1的肺血管收缩活性被NO抵消。相比之下，在预先用吲哚美辛加L - NAME处理的猪中，ET -1引起短暂的全身血管收缩，随后血管张力逐渐降低，这可能是由于除前列腺素或NO之外的血管舒张剂释放所致。
