Vasoactive effects of 8-epi-prostaglandin F(2alpha)in isolated human placental conduit and resistance blood vessels in vitro.

The effects of 8-epi-prostaglandin F(2alpha)(8-epi-PGF(2alpha)) and the thromboxane A(2)-mimetic U46619 were examined on isolated human fetal placental arteries obtained from normal pregnancies and from those complicated by pre-eclampsia. The effects of these agents were examined on both conduit and resistance arteries. 8-epi-PGF(2alpha)was found to be markedly less potent than U46619 in constricting both size vessels. Vasoconstrictor EC(50)s for 8-epi PGF(2alpha)were 4.10x10(-7) m (2.02-8.35x10(-7) m) (mean, 95 per cent CI and 2.05x10(-6) m (0.43-9.89 x10(-6) m) in conduit and resistance arteries, respectively. The maximum vasoconstriction produced by 8-epi-PGF(2alpha)(112+/-17 per cent), (relative to maximum KCl induced vasoconstriction) in conduit vessels was significantly less than that caused by U46619 (152+/-20 per cent). In resistance vessels the maximum vasoconstrictor effects to 8-epi-PGF(2alpha)(208+/-10 per cent) and U46619 (201+/-19 per cent) were similar, and in both cases significantly greater than the maximal effects seen in conduit vessels. U46619 displayed a similar vasoconstrictor potency in both conduit (EC(50)=1.21x10(-9) m, 0.58-2.51x10(-9) m) and resistance arteries [EC(50)=5.95x10(-9) m, (0.81-43.60x10(-9) m] as was found for 8-epi PGF(2alpha). 8-epi-PGF(2alpha)was equipotent in resistance arteries obtained from women with severely pre-eclamptic pregnancies (EC(50)=1.25x10(-6) m, 0.25-6.17x10(-6) m) compared with normotensive controls. However, the maximum vasoconstrictor effect induced by 8-epi-PGF(2alpha)in placental resistance arteries was significantly reduced (99+/-20 per cent) in vessels obtained from severely pre-eclamptic compared with normal pregnancies. These results indicate that 8-epi-PGF(2alpha)displays differential vasoconstrictor activity in the fetal-placental vasculature. Furthermore the vasoconstrictor effects of 8-epi-PGF(2alpha)are reduced in pre-eclampsia, the effect being selective to placental resistance vessels. This reduction may occur as a result of more serious disturbances in the placental microcirculation with the disease process in pre-eclampsia.