Indomethacin, but not oxygen tension, affects the sensitivity of isolated neonatal rabbit ductus arteriosus, but not aorta, to noradrenaline.

Abstract

The effects of increasing oxygen tension from fetal to neonatal levels and of incubation in the cyclo-oxygenase inhibitor, indomethacin, on the response of isolated rings of neonatal rabbit ductus arteriosus and aorta to noradrenaline were studied in vitro. Increasing oxygen tension did not affect the sensitivity, as measured by the pEC50, of either vessel to noradrenaline. Incubation with indomethacin increased ductal sensitivity to noradrenaline tenfold, but had no effect on the aortic response. Since indomethacin caused the ductus arteriosus to contract (by the removal of dilator prostaglandins), the effect of increased muscular tone per se on the response to noradrenaline was investigated by eliciting a contracture by potassium induced depolarisation. This procedure did not alter the vessel's sensitivity to noradrenaline and reduced its maximum response (indomethacin had increased the maximum response). It is concluded that intramurally synthesised cyclo-oxygenase products, most probably prostaglandins, attenuate the sensitivity of the ductus arteriosus to noradrenaline.