Role of cyclooxygenase-1-mediated prostacyclin synthesis in endothelium-dependent vasoconstrictor activity of porcine interlobular renal arteries
Role of cyclooxygenase-1-mediated prostacyclin synthesis in endothelium-dependent vasoconstrictor activity of porcine interlobular renal arteries
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环氧合酶-1介导的前列环素合成在猪小叶间肾动脉内皮依赖性血管收缩活性中的作用
DOI：
10.1152/ajprenal.00604.2011
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发表时间：
2012-05-01
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;Luo, Wenhong;Zhou, Yingbi
刘B，罗W，张Y，李H，朱N，黄D，周Y。环氧合酶1介导的前列环素合成在猪小叶间肾动脉内皮依赖性血管收缩活性中的作用。 Am J Physiol Renal Physiol 302：F1133-F1140，2012。首次发表于 2012 年 2 月 1 日； doi:10.1152/ajprenal.00604.2011.-本研究旨在确定猪小叶间肾动脉中的内源性内皮 B-2 受体激动剂缓激肽 (BK) 是否会诱发 PGI(2)，如果是的话，确定它将如何影响血管舒缩反应，以及参与其反应的特定环氧合酶 (COX) 亚型合成。使用 HPLC 质谱分析 PGI(2) 代谢物 6-酮基-PGF(1α) 的产生，同时通过等长力测量确定对 PGI(2) 或 BK 的血管舒缩反应。结果表明，BK 会引起 6-酮-PGF(1 α) 产生的增加，这种增加会因内皮剥脱而消除，从而消除 COX-1 的表达，或因 COX-1 的抑制而减少。有趣的是，PGI(2) 会引起强烈的收缩，这种收缩可以通过拮抗血栓素-前列腺素 (TP) 受体来阻止，并且不会通过拮抗血管舒张剂 PGI(2) (IP) 受体来增强。 IP受体激动剂MRE-269和伊洛前列素没有引起任何松弛。此外，伊洛前列素也是PGI(2)类似物，可引起收缩，对TP受体拮抗作用敏感，但程度明显低于PGI(2)。事实上，RT-PCR 或蛋白质印迹法并未在容器中检测到 IP 受体。一氧化氮合酶 (NOS) 抑制后，BK 还会引起内皮依赖性收缩，但这种收缩可被 TP 受体拮抗剂阻断。此外，抑制 COX-1（而非 COX-2）会阻碍 BK 的血管收缩活性，并加速激动剂在 NOS 完整血管中诱导的舒张。这些结果表明，在猪小叶间肾动脉中，BK 引起内皮 COX-1 介导的 PGI(2) 合成，这主要导致 TP 受体的激活和血管收缩反应，可能是由于 IP 受体介导的血管舒张活性的缺乏。此外，我们的数据表明，与伊洛前列素一样，由于结构修饰，与 PGI(2) 相比，PGI(2) 类似物对 TP 受体的影响可能会降低。
Liu B, Luo W, Zhang Y, Li H, Zhu N, Huang D, Zhou Y. Role of cyclooxygenase-1-mediated prostacyclin synthesis in endothelium-dependent vasoconstrictor activity of porcine interlobular renal arteries. Am J Physiol Renal Physiol 302: F1133-F1140, 2012. First published February 1, 2012; doi:10.1152/ajprenal.00604.2011.-This study aimed to determine whether PGI(2) would be evoked by the endogenous endothelial B-2 receptor agonist bradykinin (BK) in the porcine interlobular renal artery and, if so, to determine how it would influence the vasomotor reaction, and the specific cyclooxygenase (COX) isoform(s) involved in its synthesis. The production of the PGI(2) metabolite 6-keto-PGF(1 alpha) was analyzed with HPLC-mass spectroscopy, while vasomotor reaction to PGI(2) or BK was determined with isometric force measurement. Results showed that BK evoked an increase in the production of 6-keto-PGF(1 alpha), which was abolished by endothelial denudation that removed COX-1 expression, or was reduced by COX-1 inhibition. Interestingly, PGI(2) evoked a potent contraction, which was prevented by antagonizing thromboxane-prostanoid (TP) receptors and was not enhanced by antagonizing the vasodilator PGI(2) (IP) receptors. The IP receptor agonists MRE-269 and iloprost did not induce any relaxation. Moreover, iloprost, which is also a PGI(2) analog, caused a contraction, which was sensitive to TP receptor antagonism, but was to a significantly lesser extent than that of PGI(2). Indeed, IP receptors were not detected by RT-PCR or Western blotting in the vessel. Following nitric oxide synthase (NOS) inhibition, BK also evoked an endothelium-dependent contraction, which was blocked by TP receptor antagonism. In addition, inhibition of COX-1 (but not COX-2) impeded the vasoconstrictor activity of BK and expedited the relaxation induced by the agonist in NOS-intact vessels. These results demonstrate that in the porcine interlobular renal artery BK evokes endothelial COX-1-mediated PGI(2) synthesis, which mainly leads to the activation of TP receptors and a vasoconstrictor response, possibly due to a scarcity of vasodilator activity mediated by IP receptors. Also, our data suggested that the effect of a PGI(2) analog on TP receptors could be reduced compared with that of PGI(2) due to modified structure as with iloprost.