Figure 1.

Experimental models of PAH and their respective treatment protocols. A, B) To determine the effect of MR inhibition on Raptor and Raptor-associated signaling intermediates in remodeled pulmonary arterioles, male Sprague-Dawley (SD) rats were administered 0.9% normal saline (NS) as vehicle control (V) or MCT (50 mg/kg) by intaperitoneal (IP) injection and treated with spironolactone (25 mg/kg/d) in the drinking water (A), or SU-5416 (20 mg/kg) by subcutaneous (SQ) injection followed by chronic hypoxia (10% fraction of inspired oxygen) for 21 d and treated with eplerenone (EPL; 0.6 mg/g chow) (B). C) In a disease prevention protocol, male SD rats were administered V or MCT (50 mg/kg) and initiated treatment with Staramine-mPEG (2 mg/kg) formulated with si-Scc, Staramine-mPEG formulated with si-Raptor, or si-Raptor plus spironolactone (SPIRO; 25 mg/kg/d) that continued until completion of the protocol. D) In a disease treatment protocol, male SD rats were administered V or SU-5416 (20 mg/kg) and exposed to hypoxia (10% fraction of inspired oxygen) for 21 d followed by exposure to normoxia for 21 d. In this model, si-Raptor or si-Raptor plus SPIRO (25 mg/kg/d) was initiated on day 21 and continued until the completion of the protocol. IV, intravenous; Un, untreated.