Fetal placental vascular responses to corticotropin-releasing hormone in vitro. Effects of variation in oxygen tension

In this study, using the human placenta perfused in vitro with Krebs' bicar bonate solution, we have examined the effects of changes in oxygen tension on the vasoreactivity of fetal placental blood vessels to corticotropin rel easing hormone (CRH). Vasodilatory responses to human synthetic CRH were me asured during sub-maximal vasoconstriction of the fetal placental circulati on with prostaglandin F-2 alpha (PGF(2 alpha)) (1-100 mu M). Decreases in f etal placental arterial perfusion pressure (FAP) were obtained with CRH und er conditions of high oxygen or low oxygen tension, greater than or equal t o 450 mmHg and less than or equal to 50 mmHg, respectively. Secretion of CR H into the maternal and fetal placental circulations was measured during ch anges in oxygen tension in normal placentae and placentae from abnormal pre gnancies complicated by pre-eclampsia. The change from high to low oxygen perfusion resulted in a small increase i n the basal perfusion pressure (21 +/- 3.6 to 28.3 +/- 2.6 mmHg; (P less th an or equal to 0.001, Student's paired t-test). During high oxygen perfusio n, CRH (0.3-3000 pM) caused a concentration-dependent reduction of the PGF( 2 alpha) induced increase in FAP. However, during low oxygen perfusion, the vasodilatory effects of CRH were completely inhibited (P less than or equa l to 0.05, regression analysis, ANOVA). The effect of the NO synthase inhib itor L-nitro-omega-arginine methyl ester (L-NAME, 1-100 mu M), on basal FAP during high and low oxygen conditions was also established. Low oxygen per fusion significantly attenuated L-NAME-induced increases in perfusion press ure (P less than or equal to 0.05, regression analysis, ANOVA). Low oxygen perfusion was associated with an increase in CRH secretion into the materna l but not fetal circulation. CRH release into either the maternal or fetal circulations of abnormal placentae were not significantly different from no rmal controls. In conclusion CRH-induced vasodilatation of the fetal placental vasculature in vitro is inhibited during low oxygen perfusion. This effect may be rela ted to reduced NO production. Reduced CRH induced vasodilation is associate d with increased secretion of the CRH into the maternal but not fetal circu lation. (C) 2000 Harcourt Publishers Ltd.