内皮素-3对犬肺动静脉的作用

Effects of endothelin-3 on canine isolated pulmonary arteries and veins

阐明内皮素 3(ET 3)对肺动静脉的作用机理 .利用犬离体肺动静脉条 ,观察其张力改变 .结果可见 :①ET 3(1～ 30 μmol·L- 1)引起肺动脉舒张 (低浓度 )和收缩 (高浓度 )双向反应 ,ETB 受体激动剂IRL162 0 (1～ 30 μmol·L- 1)只引起舒张反应 ;去内皮 ,ETB 受体阻断剂IRL10 38(1μmol·L- 1)或左旋硝基精氨酸 (L NA ,10 μmol·L- 1)均使ET 3或IRL162 0所致舒张反应减弱或消失 ,ETA 受体阻断剂BQ12 3(10 μmol·L- 1)则使ET 3所致收缩反应翻转为舒张反应 ;②同浓度的ET 3和IRL162 0只引起肺静脉浓度依赖性收缩反应 ;BQ12 3可使ET 3所致收缩反应减弱 ,IRL10 38可使IRL162 0所致收缩反应减弱 ;③在BQ12 3预处理条件下给予第二剂ET 3(30 μmol·L- 1) ,肺静脉表现为舒张反应 ,吲哚美辛 (1μmol·L- 1)可使其舒张反应减弱 .本研究表明 :①存在于肺动脉平滑肌上的ETA 受体参与血管的收缩反应 ,肺动脉内皮上的ETB 受体通过释放NO参与舒张反应 ;②肺静脉平滑肌上的ETA 和ETB 受体均参与收缩反应 ,但ETB 受体所致收缩反应易脱敏 ;③在肺静脉平滑肌上可能还存在非ETA/非ETB 受体 ,通过释放舒张性PG物质参与舒张反应 .

The present study was designed to determine the effects of endothelin-3(ET-3) on canine pulmonary vasculature. The isometric tension of pulmonary arterial and venous strips were recorded. The results showed that ①ET-3(1-30 μmol·L -1) elicited biphasic responses(relaxation at 1 nmol·L -1 and contraction at 10 nmol·L -1 or higher), whereas ET B receptor agonist IRL1620(1-30 μmol·L -1)induced only relaxation in dog pulmonary arteries. The relaxations by ET-3 and IRL1620 were not affected by indomethacin, but were abolished by endothelium denudation or N G-nitro-L-arginine(10 μmol·L -1). The relaxations caused by ET-3 and IRL1620 were markedly suppressed by ET B receptor antagonist IRL1038(1 μmol·L -1). ET A receptor agonist BQ123(10 μmol·L -1) potentiated ET-3-induced relaxations and markedly suppresses ET-3-induced contractions. ②The same concentrations of ET-3 and IRL1620 produced only concentration-dependent contraction in pulmonary venous strips, respectively. The contractions induced by ET-3 and IRL1620 were significantly suppressed by BQ123 and IRL1038, respectively. ③Following pretreatment with ET A receptor blocker (BQ123 10 μmol·L -1), the second application of ET-3 (30 nmol·L -1) produced endothelium-independent relaxation, which was abolished by indomethacin(1 μmol·L -1). It is concluded that pulmonary arterial and venous responses to ET-3 can be attributed mainly to activation of ET A and ET B receptors. It appears that ET A receptors located in the vascular smooth muscle mediate contractions in the arteries and veins; ET B receptors located in the arterial endothelium mediate relaxations via release of endothelium derived nitric oxide, whereas those located in venous smooth muscle mediate contractions. Non-ET A/non-ET B receptors in the venous smooth muscle are likely to participate in prostaglandin-mediated relaxation.