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

The effects of 8-epi-prostaglandin F-2 alpha (8-epi-PGF(2 alpha)) and the t hrombosane A(2)-mimetic U46619 were examined on isolated human fetal placen tal arteries obtained from normal pregnancies and from those complicated by pre-eclampsia. The effects of these agents were examined on both conduit a nd resistance arteries. 8-epi-PGF(2 alpha) was found to be markedly less po tent than U46619 in constricting both size vessels. Vasoconstrictor EC(50)s for 8-epi PGF(2 alpha) were 4.10 x 10(-7) M (2.02-8.35 x 10(-7) M) (mean, 95 per cent CI and 2.05 x 10(-6) M (0.43-9.89 x 10(-6) M) in conduit and re sistance arteries, respectively. The masimum vasoconstriction produced by 8 -epi-PGF(2 alpha) (112 +/- 17 per cent), (relative to masimum KCl induced v asoconstriction) in conduit vessels was significantly less than that caused by U46619 (152 +/- 20 per cent). In resistance vessels the masimum vasocon strictor effects to 8-epi-PGF(2 alpha) (208 +/- 10 per cent) and U46619 (20 1 +/- 19 per cent) were similar, and in both cases significantly greater th an the maximal effects seen in conduit vessels. U46619 displayed a similar vasoconstrictor potency in both conduit [EC50 = 1.21 x 10(-9) M, 0.58-2.51 x 10(-9) M] and resistance arteries [EC50 = 5.95 x 10(-9) M] 0.81-43.60 x 1 0(-9) was was found for 8-epi PGF(2 alpha). 8-epi-PGF(2 alpha) was equipote nt in resistance arteries obtained from nomen with severely pre-eclamptic p regnancies[EC50 = 1.25 x 10(-6) M, 0.25-6.17 x 10(-6) M] compared with norm otensive controls. However, the masimum vasoconstrictor effect induced by 8 -epi-PGF(2 alpha) in placental resistance arteries was significantly reduce d (99 +/- 20 per cent) in vessels obtained from severely pre-eclamptic comp ared with normal pregnancies. These results indicate that 8-epi-PGF(2 alpha ) displays differential vasoconstrictor activity in the fetal-placental vas culature. Furthermore the vasoconstrictor effects of 8-epi-PGF(2 alpha) are reduced in pre-eclampsia, the effect being selective to placental resistan ce vessels. This reduction may occur as a result of more serious disturbanc es in the placental microcirculation with the disease process in pre-eclamp sia, (C) 2001 Harcourt Publishers Ltd Placenta (2001), 22, 526-533.