Document Detail


PKC regulates alpha(1)-adrenoceptor-mediated contractions and baseline Ca(2+) sensitivity in the uterine arteries of nonpregnant and pregnant sheep acclimatized to high altitude hypoxia.
MedLine Citation:
PMID:  20586600     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Chronic hypoxia has a profound effect on uterine artery adaptation to pregnancy. The present studies tested the hypothesis that pregnant kinase C (PKC) differentially regulates alpha(1)-adrenoceptor-mediated contractions and Ca(2+) sensitivity in the uterine arteries of nonpregnant and pregnant sheep acclimatized to high altitude hypoxia. Uterine arteries were isolated from nonpregnant (NPUA) and near-term pregnant (PUA) ewes maintained at high altitude (3801 m, Pao(2) approximately 60 torr) for 110 days. Phorbol 12,13-dibutyrate (PDBu) decreased phenylephrine-induced contractions in PUA but not in NPUA, which was partly inhibited by the PKC inhibitor GF109203X. Additionally, GF109203X shifted the concentration-response curve of phenylephrine-induced contractions to the right in PUA. In beta-escin-permeabilized arteries, Ca(2+)-induced increases in 20-kDa myosin light chain phosphorylation (MLC(20)-P) were similar in NPUA and PUA. However, Ca(2+) produced a concentration-dependent increase in the ratio of tension to MLC(20)-P in PUA, as compared with NPUA. PKC inhibition decreased Ca(2+)-induced contractions in both NPUA and PUA. PDBu induced contractions of PUA in the absence of changes in MLC(20)-P, which was not affected by PD098059. There was a significant increase in the basal activity of PKCvarepsilon in PUA, but not in NPUA, in hypoxic sheep, as compared with normoxic animals. The results demonstrate that the inhibitory effect of PKC on alpha(1)-adrenoceptor-mediated contractions of uterine arteries is preserved in pregnant sheep at high altitude. However, the PKC-mediated thin-filament regulatory pathway is upregulated, resulting in increased baseline Ca(2+) sensitivity in the uterine artery during pregnancy at high altitude.
Authors:
Daliao Xiao; Xiaohui Huang; Lawrence D Longo; Lubo Zhang
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  High altitude medicine & biology     Volume:  11     ISSN:  1557-8682     ISO Abbreviation:  High Alt. Med. Biol.     Publication Date:  2010  
Date Detail:
Created Date:  2010-06-30     Completed Date:  2010-10-21     Revised Date:  2011-08-01    
Medline Journal Info:
Nlm Unique ID:  100901183     Medline TA:  High Alt Med Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  153-61     Citation Subset:  IM; S    
Affiliation:
Center for Perinatal Biology, Department of Physiology & Pharmacology, Loma Linda University School of Medicine, California, USA. dxiao@llu.edu <dxiao@llu.edu>
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MeSH Terms
Descriptor/Qualifier:
Adaptation, Physiological / physiology
Adenosine Triphosphate / physiology
Animals
Arteries / physiology
Calcium / metabolism
Extracellular Signal-Regulated MAP Kinases / metabolism*
Female
Pregnancy
Pregnancy, Animal / physiology*
Protein Kinase C / physiology*
Receptors, Adrenergic, alpha-1 / physiology*
Sheep / physiology*
Uterine Contraction / physiology
Uterus / blood supply*
Grant Support
ID/Acronym/Agency:
HD31226/HD/NICHD NIH HHS; HL89012/HL/NHLBI NIH HHS; R01 HL082779-04/HL/NHLBI NIH HHS; R01 HL083966-04/HL/NHLBI NIH HHS; R01 HL083966-05/HL/NHLBI NIH HHS; R01 HL089012-03/HL/NHLBI NIH HHS; R01 HL089012-04/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Receptors, Adrenergic, alpha-1; 56-65-5/Adenosine Triphosphate; 7440-70-2/Calcium; EC 2.7.11.13/Protein Kinase C; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases
Comments/Corrections

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