Document Detail


Enhanced store-operated Ca²+ entry and TRPC channel expression in pulmonary arteries of monocrotaline-induced pulmonary hypertensive rats.
MedLine Citation:
PMID:  21940663     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Pulmonary hypertension (PH) is associated with profound vascular remodeling and alterations in Ca(2+) homeostasis in pulmonary arterial smooth muscle cells (PASMCs). Previous studies show that canonical transient receptor potential (TRPC) genes are upregulated and store-operated Ca(2+) entry (SOCE) is augmented in PASMCs of chronic hypoxic rats and patients of pulmonary arterial hypertension (PAH). Here we further examine the involvement of TRPC and SOCE in PH with a widely used rat model of monocrotaline (MCT)-induced PAH. Rats developed severe PAH, right ventricular hypertrophy, and significant increase in store-operated TRPC1 and TRPC4 mRNA and protein in endothelium-denuded pulmonary arteries (PAs) 3 wk after MCT injection. Contraction of PA and Ca(2+) influx in PASMC evoked by store depletion using cyclopiazonic acid (CPA) were enhanced dramatically, consistent with augmented SOCE in the MCT-treated group. The time course of increase in CPA-induced contraction corresponded to that of TRPC1 expression. Endothelin-1 (ET-1)-induced vasoconstriction was also potentiated in PAs of MCT-treated rats. The response was partially inhibited by SOCE blockers, including Gd(3+), La(3+), and SKF-96365, as well as the general TRPC inhibitor BTP-2, suggesting that TRPC-dependent SOCE was involved. Moreover, the ET-1-induced contraction and Ca(2+) response in the MCT group were more susceptible to the inhibition caused by the various SOCE blockers. Hence, our study shows that MCT-induced PAH is associated with increased TRPC expression and SOCE, which are involved in the enhanced vascular reactivity to ET-1, and support the hypothesis that TRPC-dependent SOCE is an important pathway for the development of PH.
Authors:
Xiao-Ru Liu; Ming-Fang Zhang; Na Yang; Qing Liu; Rui-Xing Wang; Yuan-Ning Cao; Xiao-Ru Yang; James S K Sham; Mo-Jun Lin
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-09-21
Journal Detail:
Title:  American journal of physiology. Cell physiology     Volume:  302     ISSN:  1522-1563     ISO Abbreviation:  Am. J. Physiol., Cell Physiol.     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2011-12-19     Completed Date:  2012-02-06     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  100901225     Medline TA:  Am J Physiol Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  C77-87     Citation Subset:  IM    
Affiliation:
Department of Physiology and Pathophysiology, Fujian Medical University, Fuzhou, Fujian Province, People's Republic of China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Calcium / metabolism,  physiology
Calcium Signaling / physiology*
Cells, Cultured
Hypertension, Pulmonary / chemically induced,  metabolism*
Male
Monocrotaline / administration & dosage*
Organ Culture Techniques
Pulmonary Artery / drug effects,  metabolism*
Rats
Rats, Sprague-Dawley
TRPC Cation Channels / biosynthesis*,  physiology
Grant Support
ID/Acronym/Agency:
R01 HL075134/HL/NHLBI NIH HHS; R01-HL-071835/HL/NHLBI NIH HHS; R01-HL-075134/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/TRPC Cation Channels; 0/TRPC4 ion channel; 0/transient receptor potential cation channel, subfamily C, member 1; 315-22-0/Monocrotaline; 7440-70-2/Calcium
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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