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.
Krylatov
A V
AV
Institute of Cardiology, Siberian Division of Russian Academy of Medical Sciences, Tomsk.
Maslov
L N
LN
Ermakov
S Yu
SY
Barzakh
E I
EI
Lasukova
O V
OV
Crawford
D
D
Ghadessy
R
R
Serebrov
V Yu
VY
D000818:Animals; D002186:Cannabinoids / Q000494:pharmacology*; D002698:Chloralose / Q000494:pharmacology; D013759:Dronabinol / Q000031:analogs & derivatives / Q000494:pharmacology; D004562:Electrocardiography; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*
D002186:Cannabinoids; D043884:Receptor, Cannabinoid, CB1; D002698:Chloralose; D013759:Dronabinol; C062018:HU 211