Modified histamine-induced NO-mediated relaxation in resistance arteries in pre-eclampsia

Abstract

We investigated the characteristic changes in histamine-induced, endothelium-derived nitric oxide (NO)-mediated relaxation in human omental resistance arteries seen in pre-eclampsia. Isometric contraction was provoked by a stable analogue of thromboxane A 2 in endothelium-intact strips from both pre-eclamptic and normotensive pregnant women. Histamine (0.3 nM–10 μM) produced a concentration-dependent relaxation of this contraction in both groups. The magnitude of the relaxation induced by histamine (1 μM) was significantly smaller in pre-eclampsia both in the presence and absence of famotidine (H 2-receptor blocker). In the presence of famotidine, l- N G-nitroarginine significantly attenuated the histamine-induced relaxation in strips from normotensive pregnant women but not in those from pre-eclamptic women. The relaxation induced by human atrial natriuretic peptide (0.1 nM–1 μM) was also significantly smaller in the pre-eclamptic group. It is concluded that the histamine-induced, endothelium-derived NO-mediated relaxation (mediated via H 1-receptors) is down-regulated in resistance arteries in pre-eclampsia and we suggest that this is due, at least in part, to an attenuation of the action of cyclic GMP in smooth muscle cells.