Cytochrome P 450-linked monooxygenase: involvement in the lamb ductus arteriosus

CO and metyrapone were tested on isolated ductus arteriosus preparations from mature fetal lambs equilibrated at low (4-12 Torr) and high (511-712 Torr) O2 partial pressure (PO2). CO completely reversed the contractile tension of the ductus at either PO2 value and was equally effective in the absence and presence of indomethacin. CO relaxation still occurred when the tissue was exposed to a gas mixture having a CO-to-O2 ratio of 0.27. The inhibitory effect of CO on the O2-contracted ductus was variably reversed by light. Metyrapone was also a relaxant agent, and its action was greater at low than at high PO2. Unlike the lamb ductus, the O2-constricted guinea pig ductus did not respond to CO (maximum CO-to-O2 ratio around 1), whereas it was relaxed by metyrapone. These findings implicate a cytochrome P450-catalyzed enzymic process in the maintenance of muscle tone of the lamb ductus arteriosus and in the contractile response of the vessel to O2.