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Description
Pulmonary arterial hypertension (PAH) is an incurable disease characterized by high pulmonary vascular resistance, pulmonary arterial pressure, and right ventricular dysfunction. PAH results in dyspnea, severe skeletal muscle dysfunction, exercise intolerance, poor quality of life, and eventually death. Discovery of therapies relies on animal models of PAH. It is therefore important that disease models exhibit the same dysfunctions seen in patients with PAH. A leading model of PAH (SU5416/hypoxia) has yet to be evaluated for skeletal muscle phenotype. OBJECTIVE To measure skeletal muscle mass, fiber type, and capillary density in the SU5416/hypoxia mouse model of PAH. METHODS Mice were randomly assigned to either an induced pulmonary hypertension (SuHx) or normoxia plus vehicle (DMSO). Pulmonary hypertension was induced in both sexes at 10 weeks of age by administration of the VEGF receptor kinase 2 inhibitor SU5416 (Sigma-Aldrich S8842) via subcutaneous injection once per week (20 mg.kg−1) and chronic exposure to normobaric hypoxia for 3 weeks (FIO2 = 0.10, Patm ∼ 745 mmHg). RESULTS No differences were present in CSA (t[28] = 0.2978, p > 0.05), capillary to fiber ratio (t[30] = 1.588, p > 0.05), or fiber type proportion (F[1,92] = 2.44e-008, p > 0.05) between DMSO and SuHx for the soleus. No differences were present in muscle mass (t[42] = 0.2052, p > 0.05), CSA (t[14] = 0.7807, p > 0.05), capillary to fiber ratio (t[14.67] = .5142, p > .05), or fiber type (F[2,48] = 4.32e-009, p > 0.05) between the two conditions for the tibialis anterior. Compared to DMSO, SuHx had low gastrocnemius CSA (p=0.0025, CIDiff95=-1766 to -215.5 μm2). There was no difference in muscle mass for the plantaris between both conditions (t[40] = 0.7873, p > 0.05). CONCLUSIONS While there was low gastrocnemius CSA in the SuHx treatment, all other variables were not different vs control. Despite demonstrating cardiovascular abnormalities, our data suggest that this model is not effective in producing the skeletal muscle phenotype of PAH.
