尿皮质素对大鼠肺动脉的舒张作用。

The relaxant effect of urocortin in rat pulmonary arteries.

作者信息

Chan Y C, Yao X Q, Lau C W, Chan F L, He G W, Bourreau J-P, Huang Y

机构信息

Department of Physiology, Chinese University of Hong Kong, Shatin, NT, Hong Kong, China.

出版信息

Regul Pept. 2004 Sep 15;121(1-3):11-8. doi: 10.1016/j.regpep.2004.03.019.

DOI:10.1016/j.regpep.2004.03.019

PMID:15256268

Abstract

Urocortin is a potent vasodilator, which plays physiological or pathophysiological roles in systemic circulation. However, little is known about its action on pulmonary circulation. The present study was aimed to characterize some cellular mechanisms underlying the relaxant effect of urocortin in isolated rat pulmonary arteries. Changes in isometric tension were measured on small vessel myographs. Urocortin inhibited U46619-induced contraction with reduction of the maximal response. Urocortin-induced relaxation was independent of the presence of endothelium. Inhibitors of nitric oxide (NO)-dependent dilator, NG-nitro-L-arginine methyl ester or 1H-[1,2,4]oxadizolo[4,3-a]quinoxalin-1-one, did not affect the relaxation. Astressin (100-500 nM), a corticotropin-releasing factor (CRF) receptor antagonist and KT5720, a protein kinase A (PKA) inhibitor reduced urocortin-induced relaxation. Urocortin produced less relaxant effect in 30 mM K+- than U46619-contracted arterial rings. Urocortin did not reduce CaCl2-induced contraction in 60 mM K+-containing solution. Ba2+ (100-500 microM) but not other K+ channel blockers reduced the relaxant responses to urocortin. Urocortin also relaxed the rings preconstricted by phorbol 12,13-diacetae in normal Krebs solution while this relaxation was less in a Ca2+-free solution. Our results show that urocortin relaxed rat pulmonary arteries via CRF receptor-mediated and PKA-dependent but endothelium/NO or voltage-gated Ca2+ channel-independent mechanisms. Stimulation of Ba2+-sensitive K+ channel may contribute to urocortin-induced relaxation. Finally, urocortin relaxed pulmonary arteries partly via inhibition of a PKC-dependent contractile mechanism.

摘要

尿皮质素是一种强效血管舒张剂，在体循环中发挥生理或病理生理作用。然而，其对肺循环的作用却知之甚少。本研究旨在阐明尿皮质素对离体大鼠肺动脉舒张作用的一些细胞机制。通过小型血管张力测定仪测量等长张力的变化。尿皮质素抑制U46619诱导的收缩，降低最大反应。尿皮质素诱导的舒张与内皮细胞的存在无关。一氧化氮（NO）依赖性舒张剂的抑制剂，NG-硝基-L-精氨酸甲酯或1H-[1,2,4]恶二唑并[4,3-a]喹喔啉-1-酮，不影响舒张。促肾上腺皮质激素释放因子（CRF）受体拮抗剂阿斯特辛（100 - 500 nM）和蛋白激酶A（PKA）抑制剂KT5720可降低尿皮质素诱导的舒张。在30 mM K⁺环境下，尿皮质素产生的舒张作用比U46619收缩的动脉环小。在含60 mM K⁺的溶液中，尿皮质素不降低氯化钙诱导的收缩。Ba²⁺（100 - 500 μM）而非其他钾通道阻滞剂可降低对尿皮质素的舒张反应。在正常Krebs溶液中，尿皮质素也可使由佛波醇12,13 - 二乙酸酯预收缩的血管环舒张，而在无钙溶液中这种舒张作用较小。我们的结果表明，尿皮质素通过CRF受体介导和PKA依赖性但不依赖内皮细胞/NO或电压门控钙通道的机制使大鼠肺动脉舒张。对Ba²⁺敏感的钾通道的刺激可能有助于尿皮质素诱导的舒张。最后，尿皮质素部分通过抑制PKC依赖性收缩机制使肺动脉舒张。