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

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 mu M) 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. 3 Although 8-bromoadenosine-3', 5'-cyclic monophosphorothioate (Sp-isomer: Sp-8-Br-cAMPS, 0.1-0.3 mhl), 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, 12=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 beta-escin-skinned strips, the pD(2) 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 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.