TY - JOUR T1 - Terguride ameliorates monocrotaline-induced pulmonary hypertension in rats JF - European Respiratory Journal JO - Eur Respir J SP - 1104 LP - 1118 DO - 10.1183/09031936.00126010 VL - 37 IS - 5 AU - R. Dumitrascu AU - C. Kulcke AU - M. Königshoff AU - F. Kouri AU - X. Yang AU - N. Morrell AU - H.A. Ghofrani AU - N. Weissmann AU - R. Reiter AU - W. Seeger AU - F. Grimminger AU - O. Eickelberg AU - R.T. Schermuly AU - S.S. Pullamsetti Y1 - 2011/05/01 UR - http://erj.ersjournals.com/content/37/5/1104.abstract N2 - 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-HTR2A/B on human lungs revealed their localisation to the vascular smooth muscle layer and quantitative RT-PCR showed 5-HTR2B 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. ER -