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We hypothesized that in preeclampsia (PE), contribution of endothelium-derived hyperpolarizing factor (EDHF) and the mechanism/s of its action differ from that in normal pregnancy (NP). We aimed to assess endothelial function and morphology in arteries from NP and PE with particular focus on EDHF. Arteries ([approximately equal to] 200 [micro] m) were dissected from subcutaneous fat biopsies obtained from women undergoing cesarean section. With the use of wire myography, responses to the endothelium-dependent agonist bradykinin (BK) were determined before and after inhibition of pathways relevant to EDHF activity. The overall responses to BK in arteries from PE (n = 13) and NP (n = 17) were similar. However, in PE, EDHF-mediated relaxation was reduced (P < 0.05). All women within the PE group were divided into two subgroups: with more (group 1) or less (group 2) than 50% reduction of EDHF-typed responses after 18-[alpha]-glycyrrhetinic acid (an inhibitor of myoendothelial gap junctions, MEGJs). The division showed that 1) MEGJs are principally involved when the EDHF contribution is reduced; and 2) when the EDHF contribution is similar to that in NP, the H202 and/or cytochrome P-450 epoxygenase products of arachidonic acid (AA), along with MEGJs, confer EDHF-mediated relaxation. In contrast, MEGJs were the main pathway for EDHF in NP. The abundant presence of MEGJs in arteries from NP but deficiency of them in PE was observed using transmission electron microscopy. We conclude that PE is associated with heterogeneous contribution of EDHF, and the mechanism behind EDHF-typed responses is mediated either by MEGJs alone or in combination with [H.sub.2][O.sub.2] or cytochrome P-450 epoxygenase metabolites of AA. gap junctions; small arteries; pregnancy

The understanding of the basis of gender differences in vascular function is of critical importance to establish gender targeted interventions in cardiovascular medicine. In this review we concentrate on the central role of the endothelium in respect to gender differences in cardiovascular physiology and pathophysiology. The role of estrogen and its receptors is introduced not only as key players in gender-related differences in incidence of cardiovascular abnormalities but also in endothelium-dependent maintenance of vascular tone through the release of endothelium-derived vasodilators and vasoconstrictors. An improved understanding of the distinct processes that confer vascular maintenance in women and men will help to develop new treatment alternatives and improve the use of existing drugs.