Effects of cannabinoids on sympathetic and parasympathetic neuroeffector transmission in the rabbit heart.
Cannabinoids elicit marked cardiovascular responses. It is not clear how peripheral effects on the autonomic nervous system contribute to these responses. The aim of the present study was to characterize the peripheral actions of cannabinoids on the autonomic innervation of the heart. Experiments were carried out on pithed rabbits. In the first series of experiments, postganglionic sympathetic cardioaccelerator fibers were stimulated electrically. The synthetic cannabinoid receptor agonists WIN55212-2 (0.005, 0.05, 0.5, and 1.5 mg kg(-1) i.v.) and CP55940 (0.003, 0.03, 0.3, and 1 mg kg(-1) i.v.) dose dependently inhibited the electrically evoked cardioacceleration. The inhibition by WIN55212-2 (0.5 mg kg(-1) i.v.) was prevented by the CB(1) cannabinoid receptor antagonist SR141716A (0.5 mg kg(-1) i.v.). WIN55212-2 (0.5 mg kg(-1) i.v.) did not change the increase in heart rate evoked by injection of isoprenaline. In the second series of experiments, preganglionic vagal fibers were stimulated electrically. WIN55212-2 (0.005, 0.05, and 0.5 mg kg(-1) i.v.) and CP55940 (0.003, 0.03, and 0.3 mg kg(-1) i.v.) dose dependently inhibited the stimulation-evoked decrease in heart rate. The inhibition produced by WIN55212-2 (0.005, 0.05, and 0.5 mg kg(-1) i.v.) was antagonized by SR141716A (0.5 mg kg(-1) i.v.). The results indicate that cannabinoids, by activating CB(1) cannabinoid receptors, inhibit sympathetic and vagal neuroeffector transmission in the heart. The mechanism of the sympathoinhibition is probably presynaptic inhibition of noradrenaline release from postganglionic sympathetic neurons. The mechanism of the inhibition of vagal activity was not clarified: cannabinoids may have an inhibitory action on both pre- and postganglionic vagal neurons.
Szabo
B
B
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Albert-Ludwigs-Universität, Freiburg, Germany. szabo@uni-frieburg.de
Nordheim
U
U
Niederhoffer
N
N
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D048588:Benzoxazines; D001794:Blood Pressure / Q000187:drug effects; D002186:Cannabinoids / Q000494:pharmacology*; D003511:Cyclohexanols / Q000494:pharmacology; D003655:Decerebrate State / Q000503:physiopathology; D004558:Electric Stimulation; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000294:innervation; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D009451:Neuroeffector Junction / Q000187:drug effects*; D010275:Parasympathetic Nervous System / Q000187:drug effects*; D011817:Rabbits; D013564:Sympathetic Nervous System / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*; D014630:Vagus Nerve / Q000502:physiology
D000318:Adrenergic beta-Agonists; D048588:Benzoxazines; D002186:Cannabinoids; D003511:Cyclohexanols; D009025:Morpholines; D009281:Naphthalenes; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; D007545:Isoproterenol