sta-2 and 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 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.

Topics: Adult; Benzimidazoles; Bradykinin; Calcium; Calcium Channel Agonists; Cyclic GMP; Cyclooxygenase Inhibitors; Endothelium, Vascular; Female; Humans; In Vitro Techniques; Mesenteric Arteries; Muscle Contraction; Muscle, Smooth; Nitric Oxide; Nitric Oxide Synthase; Nitroprusside; Omentum; Potassium; Pre-Eclampsia; Pregnancy; Substance P; Thromboxane A2; Vasodilation

Changes in the effect of histamine on the smooth muscle of resistance arteries in pre-eclampsia were investigated by measuring isometric contractions in endothelium-denuded strips of omental resistance arteries from pre-eclamptic and normotensive pregnant women (pregnancy-term matched). Histamine (0.03 -1 microM) caused concentration-dependent relaxation of the contraction induced by 9, 11-epithio-11,12-methano-thromboxane A(2) (STA(2)) in strips from both groups. Sensitivity (for pre-eclampsia: pD(2)=6.66+/-0.04, n=5 and for normotensive pregnant women: pD(2)=7.07+/-0.03, n=10, P<0.001) was lower and the maximum response (90.6+/-0.6% vs 95.5+/-1.1%, P<0.05) was smaller in strips from pre-eclamptic women. Although 8-bromoadenosine-3', 5'-cyclic monophosphorothioate (Sp-isomer: Sp-8-Br-cAMPS, 0.1 - 0.3 mM), a phosphodiesterase (PDE)-resistant activator of adenosine-3',5'-cyclic monophosphate (cyclic AMP)-dependent protein kinase, concentration-dependently attenuated the contraction induced by STA(2) in strips from both groups, the sensitivity (for pre-eclampsia: pD(2)=3.68+/-0.04, n=5 and for normotensive pregnant women: 3.94+/-0.09, n=7, P:=0.02) was lower and the maximum response (64.2+/-2.4% vs 74.9+/-4.4%, P:<0.05) was smaller in pre-eclampsia. In beta-escin-skinned strips, the pD(2) value for the contraction-inducing effect of Ca(2+) did not differ significantly between the two groups (for pre-eclampsia, n=6; for normotensive pregnant women, n=6). Thus, omental resistance arteries from human subjects with pre-eclampsia showed (i) a weaker H(2)-receptor-mediated relaxation to histamine and (ii) a weaker cyclic AMP-analogue-induced relaxation, suggesting that the reduced action of histamine may be partly due to a decreased effect of cyclic AMP.

Topics: 8-Bromo Cyclic Adenosine Monophosphate; Calcium; Cyclic AMP; Dose-Response Relationship, Drug; Female; Histamine; Humans; In Vitro Techniques; Muscle, Smooth, Vascular; Omentum; Pre-Eclampsia; Pregnancy; Thromboxane A2; Vascular Resistance; Vasoconstriction