CANNABINOIDERGIC REGULATION OF CARDIAC CONTRACTILITY DURING ISCHEMIA/REPERFUSION
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
References:
1. Litvitskyi P.F. Pathogenic and adaptive alterations in the heart during its regional ischemia and following the restoration of coronary flow // Path. Physiol. Exp. Ther. 2002. № 2. C. 2–12.
2. Debeky M.A., Gotto A.M. New life of heart/ Translation from English. Ed. R.S. Akchurin. M.: GEOTAR Miditsina, 1998. – 500 p.
3. 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.
4. Ford W.R., Honan S.A., White R., Hiley C.R. Evidence of a novel site mediating anandamide-induced negative inotropic and coronary vasodilatator responses in rat isolated hearts // Br. J. Pharmacol. 2002. Vol. 135. P. 1191–1198.
5. Cavero I., Lokhandwala M.F., Buckley J.P., Jandhyla B.S. The effect of (-)-”9-trans-tetrahydrocannabinol on myocardial contractility and venous return in anaesthetized dogs // Eur. J. Pharmacol. 1974. Vol. 29, N 1. P 74–82.
6. 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.
7. 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.
8. 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.
9. Howlett A.C., Champion T.M., Wilker G.H., Mechoulam R. Stereochemical effects of 11-OH-”8-tetrahydrocannabinol-dimethylheptyl to inhibit adenylate cyclase and bind to the cannabinoid receptor. // Neuropharmacology. 1990. Vol. 29. P. 161–165.
10. Li D.M.F. The lack of І-adrenoceptor involvement in the cardiac action of ”1-tetrahydrocannabinol in rats // Clin. Exp. Pharmacol. Physiol. 1980. Vol. 7. P. 23–29.
11. Smiley K. A., Karler R., Turkanis S. A. Effects of cannabinoids on the perfused rat heart // Res. Commun. Chem. Pathol. Pharmacol. 1976. Vol. 14. P. 659–675.
12. Mansbach R.S., Rovertti C.C., Winston E.N., Lowe J.A. Effects of the cannabinoid CB1 receptor antagonist SR141716A on the behavior of pigeons and rats // Psychopharmacology. 1996. Vol. 124. P.315–322.
13. Bouaboula M., Desnoyer N., Carayon P. et al. Gi protein modulation induced by a selective inverse agonist for the peripheral cannabinoid receptor CB2: Implication for intracellular signalization cross-regulation // Mol. Pharmacol. 1999. Vol. 55. P. 473-480.
14. Mechoulam R., Feigenbaum J.J., Lander N. et al. Enantiomeric cannabinoids: Stereospecificity of psychotropic activity // Experientia. 1990. Vol. 44. P.762-764.
15. Korth M., Engels J. Inotropic and electrophysiolgical effects of 8-substituted cyclic AMP analogues on guina-pig papillary muscle // Naunyn-Schmiedeberg’s Arch. Pharmacol. 1987. Vol. 335. P. 77–85.
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Issue: 3, 2009
Rubric: Cardiology and Functional Diagnostics
Pages: 25 — 30
Downloads: 900