Introduction: Pulmonary hypertension (PH) is a severe disease with a poor prognosis. Different forms of PH are characterized by vascular remodeling, resulting in increased vascular resistance and subsequent right heart failure. Significant progress in understanding the pathophysiology of PH has resulted in shift in therapeutic targets. Ghrelin (GHR) is a vasoactive peptide with several cardiovascular effects. We have recently described an infantile model of PH induced by monocrotaline (MCT).
Objective: The aim of this work was to establish a neonatal model of pulmonary hypertension induced by MCT and to evaluate hemodynamic and morphometric effects of GHR administration.
Methods: Wistar rats 3-day-old randomly received MCT (30mg/Kg, subcutaneous) or equal volume of vehicle (Group Ctrl). At D7, animals treated with MCT randomly received GHR (100µg/kg, subcutaneous, bid) (Group MCT-GHR) or vehicle (Group MCT) for 2 weeks. Between D21-23, animals were instrumented to evaluate the following right ventricle (RV) and left ventricle (LV) hemodynamic parameters: pressure at peak systole (Pmax), peak rates pressure rise (dP/dtmax), pressure fall (dP/dtmin) and time constant τ. At the end, heart and lungs were excised and weighted.
Results: Presented in the table as means±SE. p<0.05: a vs. Ctrl; b vs. Ctrl-GHR; c vs. MCT.
Conclusions: Administration of GHR induced an increase in body weight and attenuated hemodynamic alterations induced by MCT. GHR may present as a future candidate for therapeutic use in PH in neonatal period.