内皮素-1对家犬肺动脉的作用机制

Action mechanism of endothelin-1 on pulmonary arteries of canis familiaris ex vivo

目的探讨内皮素-1(ET-1)对家犬肺动脉的作用机制。方法利用家犬离体肺动脉标本,观察ET-1对其张力的影响。结果ET-1(1.0～30.0nmol/L)引起正常肺动脉(27例中的19例)的一过性舒张(低浓度)后持续性收缩(高浓度)的双向反应,去掉内皮可使舒张反应消失且反转为收缩反应,而其收缩反应明显增强(P<0.01)。一氧化氮合酶(NOS)抑制剂左旋硝基精氨酸预处理可使其舒张反应消失,且反转为明显增强的收缩反应(P<0.01)。ETB受体阻断剂BQ788预处理可使其舒张反应消失且反转为收缩反应(P<0.01),而收缩反应明显增强(P<0.01)。在部分正常肺动脉(27例中的8例)ET-1仅引起收缩反应,对该8例用ETA受体阻断剂BQ123预处理后亦引起舒张(低浓度)和收缩(高浓度)双向反应,并使其收缩反应明显减弱(P<0.01);前列腺素内过氧化物合成酶抑制剂吲哚美辛(IM)预处理对其舒张和收缩反应并无影响。结论在家犬肺动脉上存在ETA受体和ETB受体。ET-1作用于平滑肌上的ETA受体引起肺动脉的收缩反应;作用于内皮上的ETB受体后通过释放内皮源性一氧化氮引起肺动脉的舒张反应。

Objective To study action mechanism of endothelin （ET） -1 on pulmonary arteries of canis familiaris. Methods The pulmonary arterial strips ex vivo were used to observe the effect of ET-1 on its isometric tension. Results In 19 of 27 strips, ET-1 （ 1.0 - 30. 0 nmol/L） elicited sustained contractions after transient relaxations. ET-1 induced relaxation were abolished by endothelium-denudation to return to obviously increased contraction （P 〈0.01 ）. Pretreatment with nitric oxide synthetase （NOS） NC-nitro-L-arginine and ETB receptor blocking pharmacon BQ788 had same action as endothelium-denudation. In 8 of 27 strips, ET-1 induced only contractions, but pretreatment with ETA receptor blocking pharmacon BQ123 induced relaxation at low concentrations and contractions at high concentrations and obviously decreased contractions （P 〈0. 01 ）. Pretreatment with prostaglandin endoperoxides synthetase inhibitor indomethacin had no action on relaxation and contractions. Condusions ETA and ETB receptors exist in pulmonary artery of canis familiaris. The pulmonary arterial contractile responses to ET-1 could be attributed mainly to activation of ETA receptors; ETa receptors induced by ET-1 could revoke the pulmonary arterial relaxation responses via release of endothelium derived nitrogen monoxidum.