| Pregnancy attenuates uterine artery pressure-dependent vascular tone: role of PKC/ERK pathway. | |
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MedLine Citation:
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PMID: 16399857 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The mechanisms of adaptation of uterine artery vascular tone to pregnancy are not fully understood. The present study tested the hypothesis that pregnancy decreases the PKC-mediated Ca(2+) sensitivity of the contractile process and attenuates myogenic tone in resistance-sized uterine arteries. In pressurized uterine arteries from nonpregnant (NPUA) and near-term pregnant (PUA) sheep, we measured, simultaneously in the same tissue, vascular diameter and vessel wall intracellular Ca(2+) concentration ([Ca(2+)](i)) as a function of intraluminal pressure. In both NPUA and PUA, membrane depolarization with KCl caused a rapid increase in [Ca(2+)](i) and a decrease in diameter. A pressure increase from 20 to 100 mmHg resulted in a transient increase in diameter that was associated with an increase in [Ca(2+)](i), followed by myogenic contractions in the absence of further changes in [Ca(2+)](i). In addition, activation of PKC by phorbol 12,13-dibutyrate induced a decrease in diameter in the absence of changes in [Ca(2+)](i). Pressure-dependent myogenic responses were significantly decreased in PUA compared with NPUA. However, pressure-induced increases in [Ca(2+)](i) were not significantly different between PUA and NPUA. The ratio of changes in diameter to changes in [Ca(2+)](i) was significantly greater for pressure-induced contraction of NPUA than that of PUA. Inhibition of PKC by calphostin C significantly attenuated the pressure-induced vascular tone and eliminated the difference of myogenic responses between NPUA and PUA. In contrast, the MAPKK (MEK) inhibitor PD-098059 had no effect on NPUA but significantly enhanced myogenic responses of PUA. In the presence of PD-098059, there was no difference in pressure-induced myogenic responses between NPUA and PUA. The results suggest that pregnancy downregulates pressure-dependent myogenic tone of the uterine artery, which is partly due to increased MEK/ERK activity and decreased PKC signal pathway leading to a decrease in Ca(2+) sensitivity of myogenic mechanism in the uterine artery during pregnancy. |
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Authors:
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Daliao Xiao; John N Buchholz; Lubo Zhang |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2006-01-06 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 290 ISSN: 0363-6135 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2006 Jun |
Date Detail:
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Created Date: 2006-05-11 Completed Date: 2006-06-22 Revised Date: 2013-06-03 |
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: H2337-43 Citation Subset: IM |
Affiliation:
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Department of Physiology & Pharmacology, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA. lzhang@llu.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Arteries / physiology Blood Pressure / physiology* Calcium / metabolism Calcium Signaling / physiology Enzyme Inhibitors / pharmacology Extracellular Signal-Regulated MAP Kinases / physiology* Female Flavonoids / pharmacology Muscle Contraction / physiology Muscle Tonus / physiology* Muscle, Smooth, Vascular / physiology* Phorbol 12,13-Dibutyrate / pharmacology Pregnancy / physiology* Protein Kinase C / antagonists & inhibitors, physiology* Regional Blood Flow / physiology Sheep Signal Transduction / physiology* Uterus / blood supply* Vascular Resistance / physiology |
| Grant Support | |
ID/Acronym/Agency:
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HD 31226/HD/NICHD NIH HHS; HL 57787/HL/NHLBI NIH HHS; HL 67745/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; 0/Enzyme Inhibitors; 0/Flavonoids; 37558-16-0/Phorbol 12,13-Dibutyrate; 7440-70-2/Calcium; EC 2.7.11.13/Protein Kinase C; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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