Effects of variation in oxygen tension on responses of the human fetoplacental vasculature to vasoactive agents in vitro.

The human placenta perfused in vitro with Krebs' solution has been used to examine the effects of low oxygen tension on the vasoreactivity of the fetal placental vessels to several vasodilator and vasocontrictor autacoids. Increases in fetal arterial perfusion pressure (FAP) produced by endothelin-1 (ET-1, human), the thromboxane A2-mimetic U46619, 5-hydroxytryptamine (5-HT), angiotensin II (A II) and bradykinin (BK) were examined under conditions of high ( >or= 450 mmHg) and low <or= 50 mmHg) O2 tension. Similarly, decreases in pressure produced by adenosine triphosphate (ATP) and arachidonic acid (AA) were examined. The effects of these autacoids on the fetoplacental vasculature during low oxygen perfusion was compared to that obtained following nitric oxide synthase inhibition with N omega-nitro-L-arginine, (L-NOARG, 100 microns). Increases in FAP caused by ET-1, U46619, and 5-HT on fetoplacental blood vessels were not altered significantly at low oxygen tension, although that in response to BK was enhanced. Increases in FAP caused by A II were unchanged at low oxygen tension. ATP-induced decreases in FAP were reduced whereas AA-mediated changes were unchanged. Both low oxygen tension and L-NOARG produced an elevation in basal perfusion pressure. Perfusion of the human placenta with Krebs' solution of low oxygen tension may compromise placental vascular function. Impaired placental oxygenation may contribute to the development and severity of vasoconstriction in the placenta associated with pre-eclampsia/pregnancy induced hypertension.