A vasoconstrictor role for cyclooxygenase-1-mediated prostacyclin synthesis in mouse renal arteries
A vasoconstrictor role for cyclooxygenase-1-mediated prostacyclin synthesis in mouse renal arteries
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环加氧酶 1 介导的小鼠肾动脉中前列环素合成的血管收缩作用
DOI：
10.1152/ajprenal.00332.2013
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发表时间：
2013-11-01
影响因子：
4.2
通讯作者：
Zhou, Yingbi
中科院分区：
文献类型：
--
作者：
Liu, Bin;Zhang, Yingzhan;Zhou, Yingbi
本研究旨在探讨前列环素[前列腺素I-2(PGI-2)]是否引起小鼠肾血管收缩，如果有，其可能的机制(S)及其通过环氧合酶-1(COX-1)的合成如何影响局部血管收缩反应。实验在C57BL/6小鼠和/或COX-1缺陷者(COX-1(-/-))的血管上进行。结果表明，在肾动脉中，PGI2引起的收缩比在颈动脉中更强，而颈动脉中COX-1被认为是介导显著的内皮依赖性收缩。血栓烷-前列腺素(TP)受体激动剂U46619也有类似的结果。然而，在肾动脉，TP受体拮抗剂抑制了收缩，但不能引起对PGI2的任何松弛。此外，我们注意到内皮毒胆碱受体激动剂ACh引起PGI2代谢产物6-keto-PGF(1α)的产生增加，这一作用可被内皮剥离或COX-1(-/-)所阻止。有趣的是，COX-1(-/-)被进一步发现可以取消对TP受体拮抗敏感的力量发展，并在NO合酶抑制后导致ACh引起的增强松弛。此外，在肾动脉中，COX底物花生四烯酸引起血管收缩反应，该反应再次被COX-1(-/-)取消。同时，非选择性COX抑制对COX-1(-/-)小鼠的血管无任何影响。因此，在小鼠肾动脉中，TP受体的高表达以及血管扩张剂PGI(2)受体的少量功能参与导致了由PGI(2)引起的强大的血管收缩效应。此外，我们的数据表明，内源性COX-1介导的PGI(2)合成导致血管收缩活性，这可能是调节局部肾血管功能的内皮衍生机制的组成部分。
This study was to determine whether prostacyclin [prostaglandin I-2 (PGI2)] evokes mouse renal vasoconstriction and, if so, the underlying mechanism(s) and how its synthesis via cyclooxygenase-1 (COX-1) influences local vasomotor reaction. Experiments were performed on vessels from C57BL/6 mice and/or those with COX-1 deficiency (COX-1(-/-)). Results showed that in renal arteries PGI2 evoked contraction more potently than in carotid arteries, where COX-1 is suggested to mediate prominent endothelium-dependent contraction. A similar result was observed with the thromboxane-prostanoid (TP) receptor agonist U46619. However, in renal arteries TP receptor antagonism, which inhibited the contraction, did not result in any relaxation in response to PGI2. Moreover, we noted that the endothelial muscarinic receptor agonist ACh evoked an increase in the production of the PGI2 metabolite 6-keto-PGF(1 alpha), which was prevented by endothelial denudation or COX-1(-/-). Interestingly, COX-1(-/-) was further found to abolish a force development that was sensitive to TP receptor antagonism and result in enhanced relaxation evoked by ACh following NO synthase inhibition. Also, in renal arteries the COX substrate arachidonic acid evoked a vasoconstrictor response, which was again abolished by COX-1(-/-). Meanwhile, nonselective COX inhibition did not show any effect in vessels from COX-1(-/-) mice. Thus, in mouse renal arteries, high expression of TP receptors together with little functional involvement from the vasodilator PGI(2) receptors results in a potent vasoconstrictor effect evoked by PGI(2). Also, our data imply that endogenous COX-1-mediated PGI(2) synthesis leads to vasoconstrictor activity and this could be an integral part of endothelium-derived mechanisms in regulating local renal vascular function.