Terguride ameliorates monocrotaline-induced pulmonary hypertension in rats.
Eur Respir J
; 37(5): 1104-18, 2011 May.
Article
in En
| MEDLINE
| ID: mdl-20947677
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Lisuride
/
Dopamine Agonists
/
Serotonin 5-HT2 Receptor Antagonists
/
Hypertension, Pulmonary
/
Lung
Limits:
Adult
/
Animals
/
Female
/
Humans
/
Male
Language:
En
Journal:
Eur Respir J
Year:
2011
Document type:
Article
Affiliation country:
Germany