Mechanism of action of endothelin-1 in the canine pulmonary circulation.
Mechanism of action of endothelin-1 in the canine pulmonary circulation.
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内皮素-1在犬肺循环中的作用机制。
DOI：
10.1152/jappl.1995.79.6.2014
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Pauly,JR
中科院分区：
文献类型：
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作者：
Barman,SA;Pauly,JR
通过使用血管闭塞技术，在离体的血液灌注狗肺中研究了内皮素（ET）-1对犬肺循环中的肺血管阻力和顺应性产生影响的可能作用机制。在本研究中，ET-1(10(-8)M)通过毛细血管后血管收缩增加肺血管阻力和肺毛细血管压力。此外，ET-1降低了总血管顺应性和中室顺应性。用ETA受体拮抗剂BQ-610(10(-7)M)或蛋白激酶C抑制剂星孢菌素(10(-6)M)和calphostin C(10(-6)M)预处理完全阻断ET-1的升压作用。通过维拉帕米(10(-5)M)通过电压依赖性钙通道消除细胞外钙动员或通过百日咳毒素激发(15微克/千克)调节G蛋白信号转导对ET-1诱导的肺血管反应没有显着影响。本研究结果表明，ET-1通过ETA受体介导和蛋白激酶C激活引起犬肺循环中的肺血管收缩，可能导致细胞内钙释放。相反，ET-1诱导的肺血管反应似乎并不涉及通过电压依赖性钙通道激活或百日咳毒素敏感的G蛋白信号传导机制进入细胞外的钙。
Possible mechanisms of action by which endothelin (ET)-1 has an effect on pulmonary vascular resistance and compliance in the canine pulmonary circulation were investigated in the isolated blood-perfused dog lung by use of vascular occlusion techniques. In the present study, ET-1 (10(-8) M) increased pulmonary vascular resistance and pulmonary capillary pressure by postcapillary vasoconstriction. In addition, ET-1 decreased total vascular compliance and middle-compartment compliance. Pretreatment with the ETA receptor antagonist BQ-610 (10(-7) M) or the protein kinase C inhibitors staurosporine (10(-6) M) and calphostin C (10(-6) M) completely blocked the pressor effect of ET-1. Elimination of extracellular calcium mobilization through voltage-dependent calcium channels by verapamil (10(-5) M) or modulation of G protein signal transduction by pertussis toxin challenge (15 micrograms/kg) had no significant effect on the ET-1-induced pulmonary vascular response. The results of the present study indicate that ET-1 causes pulmonary vasoconstriction in the canine pulmonary circulation through ETA receptor mediation and protein kinase C activation, possibly leading to intracellular calcium release. In contrast, the ET-1-induced pulmonary vascular response does not appear to involve extracellular calcium entry through voltage-dependent calcium-channel activation or pertussis toxin-sensitive G protein-signaling mechanisms.