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Fluoxetine inhibits monocrotaline-induced pulmonary arterial remodeling involved in inhibition of RhoA-Rho kinase and Akt signalling pathways in rats.
MedLine Citation:
PMID:  23181278     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Activation of the small GTPase Ras homolog gene family member A (RhoA) and Rho-associated kinase (ROCK) are important in the pathogenesis of pulmonary arterial hypertension (PAH). Selective serotonin reuptake inhibitors inhibit activation of RhoA and ROCK in vitro, and ameliorate PAH and pulmonary arterial remodeling in vivo. However, little is known about whether the RhoA-ROCK signalling pathway is involved in the treatment of PAH with fluoxetine in vivo. The aim of the present study was to investigate the involvement of the RhoA-ROCK signalling pathway in the protective effect of the selective serotonin reuptake inhibitor fluoxetine against monocrotaline (MCT)-induced pulmonary arterial remodeling. MCT was applied to establish PAH in male Wistar rats. Fluoxetine was administered by gastric gavage once a day for 21 d. The results showed that MCT induced pulmonary arterial remodeling, raised the serotonylation and membrane translocation of RhoA in the lungs, and increased serotonin transporter (5-HTT), RhoA, and ROCK2 expression, and extracellular signal-regulated kinase (ERK) and Akt phosphorylation in the pulmonary arteries and the lungs. Fluoxetine markedly inhibited these MCT-induced changes. The findings suggest that fluoxetine inhibits MCT-induced pulmonary arterial remodeling in rats by inhibition of the RhoA-ROCK and Akt signalling pathways.
Authors:
Han-Ming Wang; Yun Wang; Ming Liu; Yang Bai; Xin-Hua Zhang; Ying-Xian Sun; Huai-Liang Wang
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Publication Detail:
Type:  Journal Article     Date:  2012-11-08
Journal Detail:
Title:  Canadian journal of physiology and pharmacology     Volume:  90     ISSN:  1205-7541     ISO Abbreviation:  Can. J. Physiol. Pharmacol.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372712     Medline TA:  Can J Physiol Pharmacol     Country:  Canada    
Other Details:
Languages:  eng     Pagination:  1506-15     Citation Subset:  IM    
Affiliation:
a Department of Clinical Pharmacology, College of Pharmacy, China Medical University, No. 92, the 2nd North Road, Heping District, Shenyang, 110001, China.
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