Diverse Mechanisms of Endothelium-Derived Hyperpolarizing Factor-Mediated Dilatation in Small Myometrial Arteries in Normal Human Pregnancy and Preeclampsia1
| Autor: | Karolina Kublickiene, Marius Kublickas, Henry Nisell, Natallia Luksha, Leanid Luksha |
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| Rok vydání: | 2010 |
| Předmět: |
medicine.medical_specialty
Endothelium-derived hyperpolarizing factor Endothelium Bradykinin Vasodilation Cell Biology General Medicine Biology medicine.disease Preeclampsia chemistry.chemical_compound Endocrinology medicine.anatomical_structure Reproductive Medicine chemistry Internal medicine Circulatory system cardiovascular system medicine Blood vessel Myograph |
| Zdroj: | Biology of Reproduction. 83:728-735 |
| ISSN: | 1529-7268 0006-3363 |
| Popis: | 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, H(2)O(2) 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 H(2)O(2) 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. |
| Databáze: | OpenAIRE |
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