Document Detail


Pregnancy attenuates uterine artery pressure-dependent vascular tone: role of PKC/ERK pathway.
MedLine Citation:
PMID:  16399857     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Daliao Xiao; John N Buchholz; Lubo Zhang
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2006-01-06
Journal Detail:
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:
Created Date:  2006-05-11     Completed Date:  2006-06-22     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:  H2337-43     Citation Subset:  IM    
Affiliation:
Department of Physiology & Pharmacology, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA. lzhang@llu.edu
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MeSH Terms
Descriptor/Qualifier:
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:
HD 31226/HD/NICHD NIH HHS; HL 57787/HL/NHLBI NIH HHS; HL 67745/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
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

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