beraprost and Pre-Eclampsia

It remains unclear in pre-eclampsia whether or not a functional change occurs in the role played by prostacyclin in endothelium-dependent relaxation in resistance arteries. We examined this using human omental resistance arteries (obtained from pre-eclamptic or normotensive pregnant women) in the presence of N(G)-nitro-L-arginine (L-NNA, an inhibitor of nitric oxide synthase). In endothelium-intact strips from both groups, 9,11-epithio-11,12-methano-thromboxane A(2) (STA(2), a thromboxane A(2) mimetic) produced a contraction. Diclofenac (an inhibitor of cyclooxygenase) enhanced the STA(2) contraction only in the normotensive pregnant group (1.4 times control, P < 0.01). In the presence of STA(2), bradykinin (0.1 microM) produced an endothelium-dependent relaxation in both groups, the relaxation being significantly smaller for the pre-eclamptic group (P < 0.002). Diclofenac significantly attenuated the bradykinin-induced relaxation only for the normotensive pregnant group (31 % inhibition, P < 0.001). The bradykinin-induced membrane hyperpolarization consisted of diclofenac-sensitive and -insensitive components. The former, but not the latter, was significantly smaller in pre-eclampsia (-4.3 vs. -2.6 mV, P < 0.05). The concentrations of 6-keto-PGF(1alpha) (a stable metabolite of prostacyclin) in these arteries were significantly lower in pre-eclampsia in both the absence and presence of bradykinin (about 0.2-0.4 times the normotensive pregnant value in each case, P < 0.01). By contrast, both the relaxation and the membrane hyperpolarization in response to beraprost (10 nM, a stable analogue of prostacyclin) were similar between the two groups. We conclude that, in pre-eclampsia, a reduced part is played by prostaglandins in the endothelium-dependent relaxation seen in resistance arteries and that this may be due to a reduced production of prostacyclin by the endothelium.

Topics: Adult; Arteries; Bradykinin; Cells, Cultured; Cyclooxygenase Inhibitors; Diclofenac; Electrophysiology; Endothelium, Vascular; Epoprostenol; Female; Humans; In Vitro Techniques; Membrane Potentials; Muscle, Smooth, Vascular; Omentum; Pre-Eclampsia; Pregnancy; Vascular Resistance; Vasoconstriction; Vasodilator Agents