The effects of prostaglandins, prostaglandin inhibitors, and oxygen on the closure of the ductus arteriosus, pulmonary arteries and umbilical vessels in vitro.

Abstract Three prostaglandins (PGF 2 α and PGE 1 , PGE 2 ) have been found in maternal and fetal circulation during labour. Two of these prostaglandins (PGF 2 α and PGE 2 ) are present in elevated levels in maternal circulation during labour and their presence in fetal vessels has been shown. These three prostaglandins have been tested for their effects on fetal vessels in vitro (umbilical artery and vein, ductus arteriosus, and smaller pulmonary artery). These vessels were selected as being crucial in the conversion from fetal to extra-uterine circulation in mammalian species. Responses of these vessels to the prostaglandins under varying oxygen regimes have been examined as well as their responses to prostaglandin inhibitors. Activity of vessels of varying gestational ages exposed to PGF 2 α was also examined. The following results were obtained: 1. All vessels, with the exception of pulmonary arteries, contracted in the presence of oxygen over the range 20–100mmHg pO 2 . At a pO 2 of 2 . 2. All vessels contracted in response to exogenous PGF 2 α with the exception of the pulmonary arteries which dilated. In the presence of PGF 2 α, the umbilical veins dilated under low ( 2 and contracted at higher levels. Contraction also occurred at lower levels after a period of time. 3. Although PGF 2 α was capable of causing contraction in the ductus arteriosus at near zero pO 2 , oxygen, (or possibly the products of oxygenation), appear to be required for continued contraction in the presence of PGF 2 α. A synergistic relationship between oxygen and PGF 2 α responses was found as oxygen tensions increased. A synergistic response between PGF 2 α and oxygen with umbilical arteries which did not increase with increased pO 2 was also found. Oxygen tension appeared to have little effect on the response of other vessels to PGF 2 α. 4. PGE 1 caused dilations in all vessels examined. Such dilations appearing to be independent of the oxygen regime prevailing. However, an increase in oxygen during experiments reversed any dilation caused by the prostaglandins. 5. PGE 2 caused contractions in umbilical vessels which were independent of oxygen. PGE 2 caused contraction of pulmonary arteries. However, in the ductus arteriosus, PGE 2 caused an initial contraction followed by a strong dilation. This dilation became weaker as pO 2 increased. 6. Additions of prostaglandin inhibitors (Naproxen and Indomethacin) to the bathing solution in which the ductus arteriosus and umbilical arteries were contracting (in response to PGF 2 α, or oxygen alone) caused a decrease in contractions, and sometimes a slight decrease when the vessel had been pretreated with PGF 2 α suggesting a possible need for endogenously synthesised prostaglandins for the maintenance of oxygen mediated contractions ( in vivo ). 7. Vessels responsed to PGF 2 α at an early gestational age. A role for prostaglandins and oxygen in the closure of fetal vessels is discussed.