•Rigorous methodology, including predefined primary endpoints, calculation of simple size, randomization and blinding. • Experiment plan include: a) assessment of the time course of pulmonary arterial hypertension to identify the time of disease onset, in order to start a curative treatment. b) evaluation of the efficacy and safety of treatments through: •in-vivo hemodynamics, echocardiography and bio-humoral and histological evaluation of heart, lungs, liver and kidney function and/or structure •ex-vivo analysis to assess treatments effects on macroscopic and microscopic heart remodeling and on the morphometry of the pulmonary arterial wall. •The same investigators were involved in the different steps of the experimentation to allow for a higher reproducibility and repeatability in the different procedures.