Vasoactive Effects of 8-Epi-Prostaglandin F2αin Isolated Human Placental Conduit and Resistance Blood Vessels In Vitro

Abstract

The effects of 8-epi-prostaglandin F2α(8-epi-PGF2α) and the thromboxane A2-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-PGF2αwas found to be markedly less potent than U46619 in constricting both size vessels. Vasoconstrictor EC50s for 8-epi PGF2αwere 4.10×10−7m (2.02–8.35×10−7m) (mean, 95 per cent CI and 2.05×10−6m (0.43–9.89 ×10−6m) in conduit and resistance arteries, respectively. The maximum vasoconstriction produced by 8-epi-PGF2α(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-PGF2α(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 (EC50=1.21×10−9m, 0.58–2.51×10−9m) and resistance arteries [EC50=5.95×10−9m, (0.81–43.60×10−9m] as was found for 8-epi PGF2α. 8-epi-PGF2αwas equipotent in resistance arteries obtained from women with severely pre-eclamptic pregnancies (EC50=1.25×10−6m, 0.25–6.17×10−6m) compared with normotensive controls. However, the maximum vasoconstrictor effect induced by 8-epi-PGF2αin 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-PGF2αdisplays differential vasoconstrictor activity in the fetal–placental vasculature. Furthermore the vasoconstrictor effects of 8-epi-PGF2αare 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.