Document Detail


Pregnancy upregulates large-conductance Ca(2+)-activated K(+) channel activity and attenuates myogenic tone in uterine arteries.
MedLine Citation:
PMID:  22042813     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Uterine vascular tone significantly decreases whereas uterine blood flow dramatically increases during pregnancy. However, the complete molecular mechanisms remain elusive. We hypothesized that increased Ca(2+)-activated K(+) (BK(Ca)) channel activity contributes to the decreased myogenic tone of uterine arteries in pregnancy. Resistance-sized uterine arteries were isolated from nonpregnant and near-term pregnant sheep. Electrophysiological studies revealed a greater whole-cell K(+) current density in pregnant compared with nonpregnant uterine arteries. Tetraethylammonium and iberiotoxin inhibited K(+) currents to the same extent in uterine arterial myocytes. The BK(Ca) channel current density was significantly increased in pregnant uterine arteries. In accordance, tetraethylammonium significantly increased pressure-induced myogenic tone in pregnant uterine arteries and abolished the difference in myogenic responses between pregnant and nonpregnant uterine arteries. Activation of protein kinase C produced a similar effect to tetraethylammonium by inhibiting BK(Ca) channel activity and increasing myogenic tone in pregnant uterine arteries. Chronic treatment of nonpregnant uterine arteries with physiologically relevant concentrations of 17β-estradiol and progesterone caused a significant increase in the BK(Ca) channel current density. Western blot analyses demonstrated a significant increase of the β1, but not α, subunit of BK(Ca) channels in pregnant uterine arteries. In accordance, steroid treatment of nonpregnant uterine arteries resulted in an upregulation of the β1, but not α, subunit expression. The results indicate that the steroid hormone-mediated upregulation of the β1 subunit and BK(Ca) channel activity may play a key role in attenuating myogenic tone of the uterine artery in pregnancy.
Authors:
Xiang-Qun Hu; Daliao Xiao; Ronghui Zhu; Xiaohui Huang; Shumei Yang; Sean Wilson; Lubo Zhang
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-10-31
Journal Detail:
Title:  Hypertension     Volume:  58     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-11-18     Completed Date:  2012-01-03     Revised Date:  2014-09-19    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1132-9     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Enzyme Activation / drug effects
Estradiol / pharmacology,  physiology*
Female
Ion Transport
Large-Conductance Calcium-Activated Potassium Channel beta Subunits / biosynthesis*,  genetics
Muscle Development / physiology*
Muscle Tonus
Phorbol 12,13-Dibutyrate / pharmacology
Potassium / metabolism
Pregnancy / physiology*
Progesterone / pharmacology,  physiology*
Protein Kinase C / metabolism
Sheep
Up-Regulation
Uterine Artery / physiology*
Grant Support
ID/Acronym/Agency:
DA025319/DA/NIDA NIH HHS; HL89012/HL/NHLBI NIH HHS; R01 HL089012/HL/NHLBI NIH HHS; R01 HL089012-04/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Large-Conductance Calcium-Activated Potassium Channel beta Subunits; 37558-16-0/Phorbol 12,13-Dibutyrate; 4G7DS2Q64Y/Progesterone; 4TI98Z838E/Estradiol; EC 2.7.11.13/Protein Kinase C; RWP5GA015D/Potassium
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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