The response of the lamb ductus venosus to prostaglandins and inhibitors of prostaglandin and thromboxane synthesis.

Rings of the umbilical end of the ductus venosus (the so-called sphincter) from nearterm fetal and newborn (1-3 days of age) lambs were studied in vitro at low (17-31 mm Hg) and high (504-705 mm Hg) P02. Tissues developed a modest contraction upon exposure to a high P02; however, this contraction generally was not sustained and tended to be greater in the fetus than in the newborn. In contrast, excess potassium (55 min) produced a sustained contraction whose magnitude was greater in the newborn. The cyclooxygenase inhibitor, indomethacin, contracted both the fetal and the neonatal ductus venosus; however, responses in the newborn were often not maintained. Furthermore, indomethacin enhanced the potassium response in the fetus, whereas it had no significant effect in the newborn. The thromboxane synthesis inhibitor, compound OKY-1581, was ineffective in either age group. Prostaglandin (PG) E2 and PGI 2 relaxed the ductus venosus, the former being slightly more potent. Conversely,stable PG endoperoxide analogs (9a,lla-epoxymethano and 9a,lla-methano-epoxy compounds) and PGF20 were contractile agents. Endoperoxide analogs were more effective in the newborn than the fetus and their action consistently exceeded that of PGF20. We conclude that the ductus venosus sphincter is endowed with functional muscle cells. These cells are under the influence of a relaxing product of the cyclooxygenase reaction which may be identified with either PGE2 or PGI2. This prostaglandin-mediated relaxing mechanism may contribute to prenatal patency of the vessel. Postnatal closure of the ductus venosus is unlikely to be a direct effect of oxygen on the sphincter muscle. The prostaglandin endoperoxides, however, are well suited for playing a role in the latter process.