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7 July 2010 Diverse Mechanisms of Endothelium-Derived Hyperpolarizing Factor-Mediated Dilatation in Small Myometrial Arteries in Normal Human Pregnancy and Preeclampsia
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Abstract

This ex vivo study focuses on the mechanisms of endothelium-dependent dilatation in the uterine circulation of normal pregnancy (n = 12) and in women with preeclampsia (n = 12). Arteries (internal diameter, ∼250 μm) isolated by myometrial biopsy from women undergoing planned cesarean delivery or delivery as a result of the deterioration of preeclampsia were studied using a wire myograph. Bradykinin-induced dilatation was assessed in the presence and/or absence of pharmacological inhibitors to determine the contribution of nitric oxide and endothelium-derived hyperpolarizing factor (EDHF), as well as that of EDHF-mediated pathways such as myoendothelial gap junctions (MEGJs) and products of arachidonic acid, H2O2 and cytochrome P450 2C9 (CYP2C9). Transmission electron microscopy was used to visualize morphological prerequisites for MEGJs. In normal pregnancy, EDHF through MEGJs appeared to be a predominant mediator conferring endothelium-dependent relaxation in small myometrial arteries. In preeclampsia, bradykinin-induced relaxation was reduced via compromised EDHF-type responses, in which the contribution of MEGJs became negligible. The attenuated role of MEGJs to endothelium-dependent relaxation was partly compensated through the contribution of H2O2 or other endothelium-derived relaxing factors. CYP2C9 products of arachidonic acid had no effect on EDHF-type relaxation in arteries of women with normal pregnancy or with preeclampsia. We suggest that EDHF-type responses via MEGJs are primarily targeted in small myometrial arteries in women with preeclampsia. This could significantly contribute to the impaired uteroplacental blood flow in this disorder.

Leanid Luksha, Natallia Luksha, Marius Kublickas, Henry Nisell, and Karolina Kublickiene "Diverse Mechanisms of Endothelium-Derived Hyperpolarizing Factor-Mediated Dilatation in Small Myometrial Arteries in Normal Human Pregnancy and Preeclampsia," Biology of Reproduction 83(5), 728-735, (7 July 2010). https://doi.org/10.1095/biolreprod.110.084426
Received: 25 February 2010; Accepted: 1 June 2010; Published: 7 July 2010
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