Characterization of changes in mechanical responses to histamine in omental resistance arteries in pre-eclampsia

Abstract

1. 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). 2. Histamine (0.03-1 μM) caused concentration-dependent relaxation of the contraction induced by 9,11-epithio-11,12-methano-thromboxane A2 (STA2) in strips from both groups. Sensitivity (for pre-eclampsia: pD2=6.66±0.04, n=5 and for normotensive pregnant women: pD2=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. 3. 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 STA2 in strips from both groups, the sensitivity (for pre-eclampsia: pD2=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. 4. In β-escin-skinned strips, the pD2 value for the contraction-inducing effect of Ca2+ did not differ significantly between the two groups (for pre-eclampsia, n=6; for normotensive pregnant women, n=6). 5. Thus, omental resistance arteries from human subjects with pre-eclampsia showed (i) a weaker H2-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.