Mechanisms underlying the reduced endothelium-dependent relaxation in human omental resistance artery in pre-eclampsia

1. In pre-eclampsia, a functional change occurs in the role played by endothelium-derived nitric oxide (NO) in the regulation of smooth muscle contraction in resistance arteries. We investigated the underlying mechanism in human omental resistance arteries from normotensive pregnant and pre-eclamptic women in the presence of diclofenac (an inhibitor of cyclo-oxygenase). 2. In endothelium-intact strips, the sensitivity to 9,11-epithio-11,12-methano-thromboxane A(2) (STA(2)) was significantly higher in pre-eclampsia, and this was not modified by either N-G-nitro-L-arginine (L-NNA, an inhibitor of NO synthase) or removal of the endothelium. 3. Bradykinin and substance P each produced an endothelium-dependent relaxation of the STA(2)-induced contraction in both groups, although the relaxation was significantly smaller for pre-eclampsia. L-NNA markedly attenuated the endothelium-dependent relaxation in the normotensive pregnant group but not in the pre-eclamptic group. 4. In the presence of L-NNA, the relaxation induced by Sodium nitroprusside (SNP) on the STA(2) contraction was significantly smaller for pre-eclamptic than for normotensive pregnant women. 5. In endothelium-denuded strips, the relaxation induced by 8-para-chlorophenyl thioguanosine-3',5'-cyclic monophosphate (8-pCPT-cGMP) on the STA(2) contraction was significantly less fur pre-eclampsia. 6. In beta-escin-skinned strips from both groups of women, 8-pCPT-cGMP (1-10 mu M) concentration-dependently attenuated the contraction induced by 0.5 mu M Ca2+. However, its relaxing action was significantly weaker in pre-eclampsia. 7. It is suggested that the weaker responsiveness to NO seen in strips fr om pre-eclamptic women may he partly due to a reduced smooth muscle responsiveness to cyclic GMP.