NEGATIVE CHRONOTROPIC EFFECT OF CANNABINOIDS IS DEPENDED ON THE ACTIVATION OF CARDIAC CB1 RECEPTORS
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
References:
1. Felder C.C., Veluz J.S., Williams H.L., et al. Cannabinoid agonists stimulate both receptor- and non-receptor-mediated signal transduction pathways in cells transfected with and expressing cannabinoid receptor clones // Mol. Pharmacol. 1992; Vol. 42: 838-845.
2. Howlett A.C., Barth F., Bonner T.I. et al. International Union of Pharmacology. XXVII. Classification of cannabinoid receptors // Pharmacol. Rev. 2002; 54, N 2: 161-202.
3. Pertwee R.G. Pharmacology of cannabinoid receptor ligands // Current Med. Chem. 1999; Vol. 6: 635-664.
4. Bonz A., Laser M., Kullmer S. et al. Cannabinoids acting on CB1 receptors decrease contractile performance in human atrial muscle // J. Cardiovasc. Pharmacol. 2003; Vol. 41, N 4: P. 657-664.
5. Vidrio H., Sanchez-Salvatori M.A., Medina M. Cardiovascular effects of (-)-11-OH-D8-tetrahydrocannabinol-dimethylheptyl in rats // J. Cardiovascular. Pharmacol. 1996; Vol. 28: 332-336.
6. Sander G.E., Lowe R.F., Given M.B., Giles T.D. Interactions between circulating peptides and the central nervous system in hemodynamic regulation // Am. J. Cardiol. 1989; Vol. 64: 44C-50C.
7. Krylatov A.V., Bernazkaya N.A., Maslov L.N. et al. Cannabinoid receptor activation increases cardiac resistance against arrhythmogenic influences and decreases infarction size. Russian J. Physiol. 2002; 88(5): 560-567.
8. Maslov L.N., Lasukova O.V., Krylatov A.V., Lishmanov Yu.B., Pertwee R. Alteration of inotropic function of isolated heart and extent of injury of cardiomyocytes after cannabinoid receptor activation during ischemia and reperfusion. Russian J. Physiol. 2003; 89(9): 1108-1116.
9. Cavero I., Solomon T., Buckley J.P., Jandhyla B.S. Studies on the bradycardia induced by (-)-Д9-trans-tetrahydrocannabinol in anesthetized dogs // Eur. J. Pharmacol. 1973; Vol. 22, N 3: P. 263-269.
10. Volmer R.R., Cavero I., Ertel R.J. et al. Role of central autonomic nervous system in the hypotension and bradycardia induced by (-)-Д9-trans-tetrahydrocannabinol // J. Pharm. Pharmac. 1974; Vol. 26, N 3: 186-192.
11. Randall M.D., Harris D., Kendall D.A., Ralevic V. Cardiovascular effects of cannabinoids // Pharmacol. Ther. 2002; Vol. 95, N 2: 191-202.
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Issue: 3, 2009
Rubric: Cardiology and Functional Diagnostics
Pages: 36 — 41
Downloads: 1035