Reduced function of endothelial prostacyclin in human omental resistance arteries in 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 μ m ) 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 1α (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 n m , 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.