Document Detail


Augmented EDHF signaling in rat uteroplacental vasculature during late pregnancy.
MedLine Citation:
PMID:  20817830     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
N I Gokina; O Y Kuzina; A M Vance
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-09-03
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  299     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-01     Completed Date:  2010-11-29     Revised Date:  2011-11-01    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H1642-52     Citation Subset:  IM    
Affiliation:
Dept. of Obstetrics, Gynecology, and Reproductive Sciences, College of Medicine, The Univ. of Vermont, Burlington, VT 05405, USA. Natalia.Gokina@uvm.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Apamin / pharmacology
Biological Factors / physiology*
Calcium Signaling / physiology
Charybdotoxin / pharmacology
Cyclooxygenase Inhibitors / pharmacology
Female
Indomethacin / pharmacology
Models, Animal
Nitric Oxide Synthase / antagonists & inhibitors,  metabolism
Placental Circulation / drug effects,  physiology*
Potassium Channels, Calcium-Activated / physiology
Pregnancy
Pregnancy, Animal / physiology*
Prostaglandin-Endoperoxide Synthases / metabolism
Rats
Rats, Sprague-Dawley
Signal Transduction / drug effects,  physiology*
Vasodilation / drug effects,  physiology
Grant Support
ID/Acronym/Agency:
HL-067250/HL/NHLBI NIH HHS; HL-088245/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Biological Factors; 0/Cyclooxygenase Inhibitors; 0/Potassium Channels, Calcium-Activated; 0/endothelium-dependent hyperpolarization factor; 115422-61-2/Charybdotoxin; 24345-16-2/Apamin; 53-86-1/Indomethacin; EC 1.14.13.39/Nitric Oxide Synthase; EC 1.14.99.1/Prostaglandin-Endoperoxide Synthases

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