The role of endothelin in oxygen-induced contraction of the ductus arteriosus in rabbit and rat fetuses

The role of endothelin in oxygen-induced contraction remains controversial. The present study was designed to investigate the role of endothelin in O2-induced contraction in the isolated ductal preparation of rabbit and rat, using the endothelin receptor antagonists, bosentan (antagonist for both ET-A and ET-B receptors) and BQ 485 (an ET-A selective antagonist). The ductus was isolated from fetal rabbits at 30 days of gestation (term 31 days) and fetal rats at 21 days of gestation (term 22 days). In the rabbit ductus with intact endothelium, 13% of the O2-induced contraction was inhibited by bosentan and 14% by BQ 485. In the rabbit ductus without endothelium, bosentan did not cause significant inhibition of the oxygen-induced contraction. In the rat ductus with intact endothelium, about 44% of the O2-induced contraction was inhibited by bosentan. In the rat ductus without endothelium, O2-induced contraction was 20% less than that in the ductus with intact endothelium. In the rat ductus without endothelium, bosentan further decreased the oxygen-induced contraction by about 24%. These data suggest that (1) endothelin plays a significant role in O2-induced contraction in the isolated ductus arteriosus, (2) there is a species difference in the degree of contribution of endothelin to the O2-induced ductal contraction, and (3) there is a species difference in the degree of contribution of the endothelium and vascular smooth muscle cells to the release of endothelin from the ductus arteriosus.