Rodent Models of Pulmonary Hypertension

Animal studies were approved by the Institutional Animal Care and Use Committee at Acceleron Pharma Inc., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, in accordance with ARRIVE guidelines. Adult male Sprague–Dawley (SD) and Wistar (WI) rats (150–180 gm) (Envigo, Indianapolis, IN) were used as SuHxNx and MCT rat models, respectively. The SuHxNx model was established by a single subcutaneous injection of vascular endothelial growth factor receptor antagonist semaxanib (SU5416, 20 mg/kg; Cayman Chemical) with immediate onset of exposure to normobaric hypoxia (10% O₂) for 3 weeks followed by normoxia (21% O₂) for 6 weeks as described^{34 (link),35 (link),70 (link)}. Sildenafil was obtained from Cayman Chemical. The MCT model was established by a single subcutaneous injection of MCT (60 mg/kg, Torris) followed by 4 week exposure to normoxia. Bmpr2^+/R899X mice were generated as a model of BMPR2 haploinsufficiency as described^{44 (link)}.