title: Mechanisms underlying the reduced endothelium-dependent relaxation in human omental resistance artery in pre-eclampsia.
abstract: 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 A2 (STA2) was significantly higher in pre-eclampsia, and this was not modified by either NG-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 STA2-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 STA2 contraction was significantly smaller for pre-eclamptic than for normotensive pregnant women. 5. In endothelium-denuded strips, the relaxation induced by 8-para-chlorophenyl thio-guanosine-3', 5'-cyclic monophosphate (8-pCPT-cGMP) on the STA2 contraction was significantly less for pre-eclampsia. 6. In beta-escin-skinned strips from both groups of women, 8-pCPT-cGMP (1-10 microM) concentration-dependently attenuated the contraction induced by 0.5 microM Ca2+. However, its relaxing action was significantly weaker in pre-eclampsia. 7. It is suggested that the weaker responsivene to NO seen in strips from pre-eclamptic women may be partly due to a reduced smooth muscle responsiveness to cyclic GMP.
authors.affiliation: Departments of Obstetrics and Gynecology and Pharmacology, Nagoya City University Medical School, Nagoya 467-8601, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Suzuki
authors.forename: J
authors.initials: J
authors.lastname: Kajikuri
authors.forename: K
authors.initials: K
authors.lastname: Suzumori
authors.forename: T
authors.initials: T
authors.lastname: Itoh
mesh_terms: D000328:Adult; D001562:Benzimidazoles / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000502:physiology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology*; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D009852:Omentum / Q000098:blood supply* / Q000502:physiology; D011188:Potassium / Q000378:metabolism; D011225:Pre-Eclampsia / Q000503:physiopathology*; D011247:Pregnancy; D013373:Substance P / Q000494:pharmacology; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D001562:Benzimidazoles; D002120:Calcium Channel Agonists; D016861:Cyclooxygenase Inhibitors; D009599:Nitroprusside; D009569:Nitric Oxide; D013373:Substance P; D013928:Thromboxane A2; C037866:STA 2; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; C102635:1-ethyl-2-benzimidazolinone; D011188:Potassium; D001920:Bradykinin; D002118:Calcium