Cannabidiol‐mediated RISK PI3K/AKT and MAPK/ERK pathways decreasing reperfusion myocardial damage

Figures

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  FIGURE 1. Recovery percentages at 15, 30, and 45 min after restoring flow and carbogen (reperfusion) in untreated hearts (IR) and in hearts treated 10 days before with CBD in doses of 5 mg/kg, c/24 h IP. Means ± SEM are shown considering n = 6 rats per group, *p ≤ .005 CBD versus IR

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  FIGURE 2. The graphs show (A) left ventricular pressure development (LVDP), (B) coronary perfusion pressure (CPP), (C) maximum value of the first derivative of positive ventricular pressure (+dP/dt max), and (D) first derivative of minimum negative ventricular pressure (−dP/dt min). From isolated hearts in Langendorff system from untreated (IR) rats and rats treated with CBD dose of 5 mg/kg, c/24 h, for 10 days prior to the experiment. Baseline measurements were made before reperfusion and at 15, 30, and 45 min after reperfusion, concluding the experiment at 60 min after reperfusion (n = 6) *p < .05 CBD versus IR

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  FIGURE 3. The heart rate (bpm) of the isolated hearts of untreated rats and rats treated with CBD doses of 5 mg/kg, c/24 h IP, was observed for 10 days prior to the experiment, placed in the Langendorff system. Basal responses were recorded prior to reperfusion and at 15, 30, and 45 min after reperfusion, concluding the experiment at 60 min. No significant differences in this variable were found in any temporality

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  FIGURE 4. (A) Representative sections of the ring cross section of the left ventricle (LV) animals with ischemia 45 min and reperfusion and animals treated with CBD stained with triphenyltetrazolium chloride. (B) Graph of the area of infarct/left ventricle (IA/LV) in coronary occlusion groups for 45 min with subsequent reperfusion (n = 6). The values are the means ± SEM. *p < .001 CBD versus IR

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  FIGURE 5. Western blot analysis (A) for AT1 receptor (40 kDa) and (B) for AT2 receptor (36 kDa), in left ventricle of rats submitted to surgery simulation (C), ischemia surgery for 45 min and subsequent reperfusion and those treated with CBD doses of 5 mg/kg c/24 h IP, 10 days prior to the ischemia‐reperfusion procedure. A representative western blot is shown above each graph. The intensity of the bands was quantified by densitometric analysis and normalized with the corresponding β‐Actin (47 kDa). The values are averages ± SEM (n = 3). (A) *p < .05 IR versus C and CBD; (B) *p < .05 CBD versus C and IR

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  FIGURE 6. Western blot analysis (A) for the Akt/PKB protein (57 kDa) and (B) its phosphorylated p‐Akt form (54 kDa); (C) densitometry of the MAPK/ERK1/2 protein (42/44 kDa) and (D) its phosphorylated p‐ERK1/2 form (44/42 kDa), in the left ventricle of rats subjected to surgical simulation (C), ischemia surgery for 45 min and subsequent reperfusion (IR) and those treated with CBD doses of 5 mg/kg c/24 h IP, 10 days prior to the ischemia‐reperfusion procedure. A representative western blot is shown above each graph. The intensity of the bands was quantified by densitometric analysis and normalized with the corresponding β‐Actin (47 kDa). The values are averages ± SEM (n = 3). (A) *p < .05 CBD versus IR and C and # p < .05 IR versus C and CBD; (B) *p < .05 CBD versus C and IR: (C, D)* versus C and IR