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.