Document Detail


Chronic hypoxia increases pressure-dependent myogenic tone of the uterine artery in pregnant sheep: role of ERK/PKC pathway.
MedLine Citation:
PMID:  19376810     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Chronic hypoxia during pregnancy has profound effects on uterine artery (UA) contractility and attenuates uterine blood flow. The present study tested the hypothesis that chronic hypoxia inhibits the pregnancy-induced reduction in pressure-dependent myogenic tone of resistance-sized UAs. UAs were isolated from nonpregnant ewes (NPUAs) and near-term pregnant ewes (PUAs) that had been maintained at sea level (approximately 300 m) or at high altitude (3,801 m) for 110 days. In normoxic animals, the pressure-dependent myogenic response was significantly attenuated in PUAs compared with NPUAs. Hypoxia significantly increased myogenic tone in PUAs and abolished its difference between PUAs and NPUAs. Consistently, there was a significant increase in PKC-mediated baseline Ca(2+) sensitivity of PUAs in hypoxic animals. Hypoxia significantly increased phorbol 12,13-dibutyrate (PDBu)-induced contractions in PUAs but not in NPUAs. Whereas the inhibition of ERK1/2 by PD-98059 potentiated PDBu-mediated contractions of PUAs in normoxic animals, it failed to do so in hypoxic animals. Hypoxia decreased ERK1/2 expression in PUAs. PDBu induced membrane translocation of PKC-alpha and PKC-epsilon. Whereas there were no significant differences in PKC-alpha translocation among all groups, the translocation of PKC-epsilon was significantly enhanced in NPUAs compared with PUAs in normoxic animals, and hypoxia significantly increased PKC-epsilon translocation in PUAs. In the presence of PD-98059, there were no significant differences in PDBu-induced PKC-epsilon translocation among all groups. Treatment of PUAs isolated from normoxic animals with 10.5% O(2) for 48 h ex vivo significantly increased PDBu-induced contractions and eliminated its difference between PUAs and NPUAs. The results suggest that hypoxia upregulates pressure-dependent myogenic tone through its direct effect in suppressing ERK1/2 activity and increasing the PKC signal pathway, leading to an increase in the Ca(2+) sensitivity of the myogenic mechanism in the UA during pregnancy.
Authors:
Katherine Chang; 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     Date:  2009-04-17
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  296     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-05-27     Completed Date:  2009-07-17     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H1840-9     Citation Subset:  IM    
Affiliation:
Center for Perinatal Biology, Department of Physiology and Pharmacology, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA.
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MeSH Terms
Descriptor/Qualifier:
Altitude
Animals
Anoxia / metabolism*,  physiopathology*
Arteries / drug effects,  enzymology*
Blood Pressure / physiology
Calcium / metabolism
Carcinogens / pharmacology
Chronic Disease
Enzyme Inhibitors / pharmacology
Female
Flavonoids / pharmacology
MAP Kinase Signaling System / physiology*
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3 / metabolism
Phorbol 12,13-Dibutyrate / pharmacology
Placental Circulation / physiology*
Pregnancy
Protein Kinase C-alpha / metabolism
Protein Kinase C-epsilon / metabolism
Sheep
Uterus / blood supply
Vascular Resistance / physiology
Vasoconstriction / drug effects,  physiology
Grant Support
ID/Acronym/Agency:
HD-31226/HD/NICHD NIH HHS; HL-89012/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; 0/Carcinogens; 0/Enzyme Inhibitors; 0/Flavonoids; 37558-16-0/Phorbol 12,13-Dibutyrate; 7440-70-2/Calcium; EC 2.7.11.13/Protein Kinase C-alpha; EC 2.7.11.13/Protein Kinase C-epsilon; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3
Comments/Corrections

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