Terguride dose-dependently inhibited proliferation of pulmonary artery smooth muscle cells and prevented the development and progression of monocrotaline-induced pulmonary hypertension in rats.
Does terguride improve monocrotaline-induced pulmonary hypertension in rats and inhibit proliferation of human PASMCs?
Terguride inhibits serotonin-induced vasoconstriction and PASMC proliferation, preventing the development and progression of pulmonary hypertension in a rat model.
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.
Dumitrascu et al. (Thu,) conducted a other in Pulmonary arterial hypertension. Terguride was evaluated on Development and progression of monocrotaline-induced pulmonary hypertension and PASMC proliferation. Terguride dose-dependently inhibited proliferation of pulmonary artery smooth muscle cells and prevented the development and progression of monocrotaline-induced pulmonary hypertension in rats.