Effects of cannabidiol on infarct size and postischemic myocardial dysfunction; mechanisms involved

SEPULVEDA F; FANTINELLI JC; MOSCA SM; GONZÁLEZ ARBELÁEZ LF

Congreso; Reunión anual organizado por la Sociedad Argentina de Fisiología, la Sociedad Argentina de Investigaciones Clínicas y la Sociedad Argentina de Inmunología.; 2020

Background: Cannabidiol (CBD) is a non psychoactivephytocannabinoid with recognized anti-inflammatory activity. Our aim was to determinethe effects of acute treatment of CBDon myocardial postichemic alterations and the mechanisms involved.Methods: Isolated Wistar rats hearts were isovolumicallyperfused through Langendorff system with Ringer´s solution (pH=7.4, 37°C) andpaced at 280 ± 10 beats/min. After 20 min of stabilization,the following experimental protocols were performed: Non-ischemic control(NIC):110 min of perfusion; Ischemic control (IC): 30 min of normothermic globalischemia and 60 min of reperfusion (R);CBD group: 0.25µM CBD was administeredduring the first 10 min of R. Infarct size (IS)was determined by TTC staining. Systolic function wasassessed by left ventricular developed pressure (LVDP) and +dP/dtmaxand diastolic function by left ventricular end diastolic pressure (LVEDP) and -dP/dtmax.The expression of phosphorylated forms of eNOS, PKCε, Akt and thecontent of cannabinoid receptor 2 (CB2) were determined by western blot. Results: CBD significantly decreased IS (7 ± 1 % vs. 31± 2 % in IC) and improved the post-ischemic recovery of myocardial function. At60 min of R, LVDP was 56 ± 8 % and +dP/dtmax  55 ± 8 % vs. 17 ± 3 %  and 15 ± 4 % in IC,respectively; LVEDP = 18 ± 3 mmHg vs. 52 ± 4 mmHg in IC; -dP/dtmax =58 ± 9 % vs. 14 ± 4 % in IC. The expression of P-eNOS andP-Akt decreased approximately 30% of NIC value (considered as 100 %) in IC and increasedapproximately 60% in CBD group. The expression of P-PKCε decreasedapproximately 50% in IC and increased a 40% in CBD group. The content of CB2 receptorsdiminished 30 % in IC hearts and increased 20 % in CBD treated hearts. Conclusions: The data demonstrate that CBD reduces the cell deathand systolic and diastolic post-ischemic dysfunction inducedby ischemia-reperfusion. These beneficial actions appear mediated by Akt/PKCe/eNOS-dependent pathways through CB2 receptors.