| Chronic hypoxia increases pressure-dependent myogenic tone of the uterine artery in pregnant sheep: role of ERK/PKC pathway. | |
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MedLine Citation:
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PMID: 19376810 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Katherine Chang; Daliao Xiao; Xiaohui Huang; Lawrence D Longo; Lubo Zhang |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-04-17 |
Journal Detail:
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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:
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Created Date: 2009-05-27 Completed Date: 2009-07-17 Revised Date: 2010-09-27 |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H1840-9 Citation Subset: IM |
Affiliation:
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Center for Perinatal Biology, Department of Physiology and Pharmacology, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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HD-31226/HD/NICHD NIH HHS; HL-89012/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Carcinogens; 0/Enzyme Inhibitors; 0/Flavonoids; 0/PD 98059; 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 | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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