Effects of the peripheral CB1 receptor antagonist JD5037 in mono— and polytherapy with the AMPK activator metformin in a monocrotaline-induced rat model of pulmonary hypertension

Figures

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  FIGURE 1. Influence of pulmonary hypertension, metformin (MET), JD5037 (JD) and/or their combination on right ventricular systolic pressure (RVSP), Fulton’s index (RV/(LV + S)) and oxygen saturation in monocrotaline-induced pulmonary hypertensive (PH) rats and their normotensive controls (CTR). MET (100 mg/kg), JD5037 (3 mg/kg) or their combination were administered by oral gavage once daily for 21 days; controls received vehicles instead. Data are expressed as mean ± SEM; n = 9–20; ***p < 0.001 significantly different from CTR + veh; ∇ p < 0.05; ∇∇ p < 0.01 significantly different from PH + veh. RV–right ventricle; LV + S–left ventricle + interventricular septum.

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  FIGURE 2. Influence of pulmonary hypertension, metformin (MET), JD5037 (JD) and/or their combination on right ventricular remodeling in monocrotaline-induced pulmonary hypertensive (PH) rats and their normotensive controls (CTR). Representative hematoxylin and eosin-stained right ventricle images (100x and 400x magnification); quantitative evaluation is provided in Table 2. MET (100 mg/kg), JD5037 (3 mg/kg) or their combination were administered by oral gavage once daily for 21 days; controls received vehicles (veh) instead.

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  FIGURE 3. Influence of pulmonary hypertension, metformin (MET), JD5037 (JD) and/or their combination on pulmonary remodeling in monocrotaline-induced pulmonary hypertensive (PH) rats and their normotensive controls (CTR). (A) pulmonary artery vascular wall thickness, (B) lung hypertrophy index (expressed as lung weight to body weight) and expression of (C) transforming growth factor β1 (TGF-β1) and (D) galectin-3 (Gal-3) determined by Western blot (WB) technique, (E) representative hematoxylin and eosin-stained lung images (200x magnification). β-actin served as a loading control in WB. Arrows on images show the location of the vessels. MET (100 mg/kg), JD5037 (3 mg/kg) or their combination were administered by oral gavage once daily for 21 days; controls received vehicles (veh) instead. Data are expressed as mean ± SEM; n = 9–20 (A–B), n = 5 (C,D); *p < 0.05; **p < 0.01; ***p < 0.001 significantly different from CTR + veh.