title: Augmented EDHF signaling in rat uteroplacental vasculature during late pregnancy.
abstract: A successful pregnancy outcome relies on extensive maternal cardiovascular adaptation, including enhanced uteroplacental vasodilator mechanisms. The objective of the present study was to determine the contribution of the endothelium-derived hyperpolarizing factor (EDHF) signaling in pregnancy-enhanced uterine vasodilation, to define the role of Ca(2+)-activated K(+) channels in mediating EDHF effects, and to explore the impact of endothelial Ca(2+) signaling in pregnancy-specific upregulation of EDHF. Fura 2-based measurements of smooth muscle cell (SMC) and endothelial cell cytosolic Ca(2+) concentration ([Ca(2+)](i)) were performed simultaneously with measurements of the diameter of uterine radial arteries from nonpregnant (NP) and late pregnant (LP) rats. Changes in SMC membrane potential of pressurized arteries from LP rats were assessed using glass microelectrodes. After blockade of nitric oxide and prostacyclin production, a cumulative application of ACh induced rapid and effective dilatation of uterine vessels from both NP and LP rats. This vasodilation was associated with SMC hyperpolarization and SMC [Ca(2+)](i) reduction and was abolished by a high-K(+) solution, demonstrating that N(G)-nitro-L-arginine (L-NNA)- and indomethacin-resistant responses are attributable to EDHF. Pregnancy significantly potentiates EDHF-mediated vasodilation in part due to enhanced endothelial Ca(2+) signaling. L-NNA- and indomethacin-resistant responses were insensitive to iberiotoxin but abolished by a combined treatment with apamin and charybdotoxin, supporting the key role of small- and intermediate-conductance K(+) channels in mediating EDHF signaling in the maternal uterine resistance vasculature.
authors.affiliation: Dept. of Obstetrics, Gynecology, and Reproductive Sciences, College of Medicine, The Univ. of Vermont, Burlington, VT 05405, USA. Natalia.Gokina@uvm.edu
authors.forename: N I
authors.initials: NI
authors.lastname: Gokina
authors.forename: O Y
authors.initials: OY
authors.lastname: Kuzina
authors.forename: A M
authors.initials: AM
authors.lastname: Vance
mesh_terms: D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001685:Biological Factors / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology; D018999:Charybdotoxin / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D023421:Models, Animal; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D021041:Placental Circulation / Q000187:drug effects / Q000502:physiology*; D024681:Potassium Channels, Calcium-Activated / Q000502:physiology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D001685:Biological Factors; D016861:Cyclooxygenase Inhibitors; D024681:Potassium Channels, Calcium-Activated; C067410:endothelium-dependent hyperpolarization factor; D018999:Charybdotoxin; D001030:Apamin; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases; D007213:Indomethacin
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