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: Y Suzuki, J Kajikuri, K Suzumori, T Itoh
• Journal: The Journal of physiology (J Physiol) Vol. 527 Pt 1 Pg. 163-74 (Aug 15 2000) ISSN: 0022-3751 [Print] England
• PMID: 10944179 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzimidazoles
• Calcium Channel Agonists
• Cyclooxygenase Inhibitors
• Nitroprusside
• Nitric Oxide
• Substance P
• Thromboxane A2
• STA 2
• Nitric Oxide Synthase
• Cyclic GMP
• 1-ethyl-2-benzimidazolinone
• Potassium
• Bradykinin
• Calcium

Topics

• Adult
• Benzimidazoles (pharmacology)
• Bradykinin (pharmacology)
• Calcium (metabolism)
• Calcium Channel Agonists (pharmacology)
• Cyclic GMP (analogs & derivatives, physiology)
• Cyclooxygenase Inhibitors (pharmacology)
• Endothelium, Vascular (drug effects, physiology)
• Female
• Humans
• In Vitro Techniques
• Mesenteric Arteries (drug effects, physiology)
• Muscle Contraction (drug effects, physiology)
• Muscle, Smooth (drug effects, physiology)
• Nitric Oxide (physiology)
• Nitric Oxide Synthase (antagonists & inhibitors)
• Nitroprusside (pharmacology)
• Omentum (blood supply, physiology)
• Potassium (metabolism)
• Pre-Eclampsia (physiopathology)
• Pregnancy
• Substance P (pharmacology)
• Thromboxane A2 (analogs & derivatives, pharmacology)
• Vasodilation (drug effects, physiology)