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CANNABINOIDERGIC REGULATION OF CARDIAC CONTRACTILITY DURING ISCHEMIA/REPERFUSION // Tomsk State Pedagogical University Bulletin. 2009. Issue 3 (81). P. 25-30

Authors studied an impact of selective ligands of cannabinoid (CB) receptors on the contractility of the isolated perfused rat heart during global ischemia and reperfusion. A perfusion by solution containing the selective CB-agonist HU-210 exacerbated a cardiac contractility dysfunction. This cannabinoid decreased the left ventricular developed pressure, the maximal rate of contraction and relaxation of the heart during reperfusion but had no effect on the heart rate and the end diastolic pressure. Negative inotropic effect of HU-210 was transient and disappeared after 5 min reperfusion. The pretreatment with the selective CB1 receptor antagonist SR141716A and the selective CB2 receptor antagonist SR144528 had no effect on the myocardial contractility during reperfusion. In conclusion, the present results indicate that CB receptor stimulation can exacerbate reperfusion contractility dysfunction of the heart. Endogenous cannabinoids are not involved in the development of myocardial contractility dysfunction during ischemia/reperfusion of the heart.

Keywords: cannabinoid receptors, cardiac contractility, ischemia, reperfusion, isolated heart

NEGATIVE CHRONOTROPIC EFFECT OF CANNABINOIDS IS DEPENDED ON THE ACTIVATION OF CARDIAC CB1 RECEPTORS // Tomsk State Pedagogical University Bulletin. 2009. Issue 3 (81). P. 36-41

It has been found that intravenous administration of cannabinoids (ACPA, anandamide, methanandamide) solubilized in the mixture (cremophore EL : ethanol : 0,9% NaCl, 1:1:18) and Tocris water soluble emulsion of the same cannabinoids induced a completely identical negative chronotropic effect in chloralose-anesthetized rats. The selective CB1 and CB2 receptor agonist HU-210 (0.1 mg/kg) also induced a negative chronotropic effect in rats. Pretreatment with the CB1 receptor antagonist SR141716A (1 mg/kg) completely abolished this effect of HU-210. The CB2 receptor antagonist SR144528 (1 mg/kg) had no effect on the HU-210-induced bradycardia. Pretreatment with the ganglion blocker hexamethonium (10 mg/kg) also did not eliminate a negative chronotropic effect of HU-210 and ACPA. A 10-min perfusion of isolated rat heart by Krebs-Heseleit solution containing HU-210 in a final concentration 100 nM/L induced a decrease in the heart rate. It has been concluded that negative chronotropic effect of cannabinoids is mediated via an activation of cardiac CB1 receptors.

Keywords: cannabinoids, heart rhythm