Document Detail

Terguride ameliorates monocrotaline-induced pulmonary hypertension in rats.
MedLine Citation:
PMID:  20947677     Owner:  NLM     Status:  MEDLINE    
Pulmonary arterial hypertension (PAH) is a life-threatening disease characterised by vasoconstriction and remodelling of the pulmonary vasculature. The serotonin (5-hydroxytryptamine (5-HT)) pathway has been shown to play a major role in the pathogenesis of PAH, but pharmacological modulation of this pathway for treatment of PAH is, to date, at a pre-clinical level. Terguride is a 5-HT receptor (5-HTR) antagonist that is well tolerated and clinically approved for ovulation disorders. Immunohistochemistry against 5-HTR(₂A/B) on human lungs revealed their localisation to the vascular smooth muscle layer and quantitative RT-PCR showed 5-HTR(₂B) upregulation in pulmonary artery smooth muscle cells (PASMC) isolated from PAH patients. Proliferation and migration of cultured primary human PASMC were dose-dependently blocked by terguride. Therapeutic 5-HT signalling inhibition was 1) demonstrated in isolated, ventilated and perfused rat lungs and 2) by chronic terguride treatment of rats with monocrotaline (MCT)-induced pulmonary hypertension in a preventive or curative approach. Terguride inhibited proliferation of PASMCs and abolished 5-HT-induced pulmonary vasoconstriction. Chronic terguride treatment prevented dose-dependently the development and progression of MCT-induced PAH in rats. Thus, terguride represents a valuable novel therapeutic approach in PAH.
R Dumitrascu; C Kulcke; M Königshoff; F Kouri; X Yang; N Morrell; H A Ghofrani; N Weissmann; R Reiter; W Seeger; F Grimminger; O Eickelberg; R T Schermuly; S S Pullamsetti
Related Documents :
19634077 - Pathology of pulmonary arterial hypertension.
1446407 - Analysis of factors in hypertension: change of membrane fluidity in the arteries of spo...
19958397 - Schistosomiasis associated pulmonary hypertension.
6641227 - Pathogenesis of pulmonary hypertension in rheumatic heart disease.
24436897 - Morphometric analysis of the middle meningeal artery organization in humans-embryologic...
17282697 - A computer simulation of blood flow in arterial networks, including blood non-newtonian...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-10-14
Journal Detail:
Title:  The European respiratory journal     Volume:  37     ISSN:  1399-3003     ISO Abbreviation:  Eur. Respir. J.     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-05-02     Completed Date:  2011-08-31     Revised Date:  2013-05-23    
Medline Journal Info:
Nlm Unique ID:  8803460     Medline TA:  Eur Respir J     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  1104-18     Citation Subset:  IM    
University of Giessen Lung Center, Germany.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Cell Proliferation / drug effects
Cells, Cultured
Dopamine Agonists / therapeutic use*
Hypertension, Pulmonary / chemically induced,  drug therapy*,  pathology
Lisuride / analogs & derivatives*,  therapeutic use
Lung / drug effects*,  pathology,  physiopathology
Lung Transplantation
Monocrotaline / pharmacology
Muscle, Smooth, Vascular / drug effects,  pathology,  physiopathology
Pulmonary Artery / drug effects,  pathology,  physiopathology
Serotonin 5-HT2 Receptor Antagonists / pharmacology*
Reg. No./Substance:
0/Dopamine Agonists; 0/Serotonin 5-HT2 Receptor Antagonists; 18016-80-3/Lisuride; 21OJT43Q88/dironyl; 315-22-0/Monocrotaline
Comment In:
Expert Opin Ther Targets. 2011 Nov;15(11):1333-5   [PMID:  21762037 ]

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

Previous Document:  The effect of ambient air pollution on exhaled nitric oxide in the Children's Health Study.
Next Document:  Clinical management of tuberculosis and HIV-1 co-infection.