Ductus arteriosus: involvement of a sarcolemmal cytochrome P-450 in O2 constriction?

Abstract

Our previous studies implicate a cytochrome P-450-based mechanism in the constrictor response of the ductus arteriosus to oxygen. The present experiments were conducted on saponin-skinned strips of ductal muscle from mature fetal lambs to determine the location, sarcolemmal versus intracellular, of this cytochrome and to obtain a better insight into the sequence of events underlying the action of oxygen. Skinned preparations contracted to free Ca2+ over the range between 0.1 and 5–10 μM (pCa 7 to 5). In contrast, oxygen (Po2, 608–690 Torr; 1 Torr = 133.3 Pa) had no significant effect, both in the absence and presence of 10 μM calcium. Carbon monoxide, tested as pure CO or a CO–O2 mixture (ratio 0.28), did not relax preparations maximally contracted with calcium. These findings indicate that oxygen exerts its effect on the plasma membrane of ductus muscle cells and that a membrane-bound cytochrome P-450 mechanism likely functions as the signal transducer for oxygen in the formation of a constrictor agent.Key words: ductus arteriosus closure, chemically skinned muscle, second messenger.