EFFECTS OF CANNABIDIOL ON INFARCT SIZE AND POSTISCHEMIC MYOCARDIAL DYSFUNCTION: MECHANISMS INVOLVED

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

Buenos Aires

Congreso; Reunión anual Conjunta de la Sociedad Argentina de Fisiología SAFIS 202; 2020

Background: Cannabidiol (CBD) is a non psychoactive phytocannabinoid with recognized anti-inflammatory activity. Our aim was to determine the effects of acute treatment of CBD on myocardial postichemic alterations and the mechanisms involved.Methods: Isolated Wistar rats hearts were isovolumically perfused through Langendorff system with Ringer´s solution (pH=7.4, 37°C) and paced 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 global ischemia and 60 min of reperfusion (R);CBD group: 0.25µM CBD was administered during the first 10 min of R. Infarct size (IS) was determined by TTC staining. Systolic function was assessed by left ventricular developed pressure (LVDP) and +dP/dtmax and diastolic function by left ventricular end diastolic pressure (LVEDP) and -dP/dtmax. The expression of phosphorylated forms of eNOS, PKCε, Akt and the content 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. At 60 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 and P-Akt decreased approximately 30% of NIC value (considered as 100 %) in IC and increased approximately 60% in CBD group. The expression of P-PKCε decreased approximately 50% in IC and increased a 40% in CBD group. The content of CB2 receptors diminished 30 % in IC hearts and increased 20 % in CBD treated hearts. Conclusions: The data demonstrate that CBD reduces the cell death and systolic and diastolic post-ischemic dysfunction induced by ischemia-reperfusion. These beneficial actions appear mediated by Akt/PKC/eNOS-dependent pathways through CB2 receptors.