Negative chronotropic effect of cannabinoids and their water-soluble emulsion is related to activation of cardiac CB1 receptors

Intravenous injection of cannabinoids dissolved in cremophore EL:ethanol:NaCl mixture and water-soluble emulsion of the same cannabinoids caused identical negative chronotropic effects in chloralose-narcotized rats. Selective CB1 and CB2 receptor antagonist HU-210 also induced a negative chronotropic effect in rats, while pre-injection of CB1 receptor antagonist SR 141716A completely abolished this effect of HU-210. Selective CB2 receptor antagonist SR 144528 had no effect on HU-210-induced bradycardia. Preinjection of ganglioblocker hexamethonium also did not abolish the negative chronotropic effect of HU-210 and ACPA. Perfusion of isolated rat heart with Krebs-Henseleit solution containing HU-210 in a final concentration of 100 nM reduced heart rate. It was shown that the negative chronotropic effect of cannabinoids is mediated through activation of cardiac CB1 receptors.