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Significance of cardiac cannabinoid receptors in regulation of cardiac rhythm, myocardial contractility, and electrophysiologic processes in heart

  • Animal Physiology
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Abstract

Intravenous administration of cannabinoid (CB) receptor agonists (HU-210, 0.1 mg/kg; ACPA, 0.125 mg/kg; methanandamide, 2.5 mg/kg; and anandamide, 2.5 mg/kg) induced bradycardia in chloralose-anesthetized rats irrespective of the solubilization method. Methanandamide, HU-210, and ACPA had no effect on the electrophysiological activity of the heart, while anandamide increased the duration of the QRS complex. The negative chronotropic effect of HU-210 was due to CB1 receptor activation since it was not observed after CB1 receptor blockade by SR141716A (1 mg/kg intravenously) but was present after pretreatment with CB2 receptor antagonist SR144528 (1 mg/kg intravenously). CB receptor antagonists SR141716A and SR144528 had no effect on cardiac rhythm or ECG indices. Hence, in the intact heart, endogenous CB receptor agonists are not involved in the regulation of cardiac rhythm and electrophysiological processes. The chronotropic effect of CBs was independent of the autonomic nervous system because it remained significant after autonomic ganglion blockade by hexamethonium (1 mg/kg intravenously). CB receptor activation by HU-210 (0.1 and 1 μM) in vitro decreased the rate and force of isolated heart contractions, the rates of contraction and relaxation, and end diastolic pressure. The negative chronotropic effect of HU-210 was less pronounced in vitro than in vivo. The maximum inotropic effect of HU-210 was reached at the concentration of 0.1 μM.

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Authors and Affiliations

  1. Tomsk State Pedagogical University, Komsomolsky prosp. 75, Tomsk, 634041, Russia

    A. V. Krylatov, L. N. Maslov & E. I. Barzakh

  2. Institute of Cardiology, Tomsk Research Center, Siberian Division, Russian Academy of Medical Sciences, ul. Kievskaya 111, Tomsk, 634050, Russia

    A. V. Krylatov, L. N. Maslov & O. V. Lasukova

  3. Siberian State Medical University, Moskovskii trakt 2, Tomsk, 634041, Russia

    S. Yu. Ermakov

  4. Tocris Cookson, Northpoint, Fourth Way, Bristol, BS 11 8TA, UK

    D. Crawford

  5. University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK

    R. G. Pertwee

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  1. A. V. Krylatov
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  2. L. N. Maslov
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  3. S. Yu. Ermakov
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  4. O. V. Lasukova
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  5. E. I. Barzakh
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Original Russian Text © A.V. Krylatov, L.N. Maslov, S.Yu. Ermakov, O.V. Lasukova, E.I. Barzakh, D. Crawford, R.G. Pertwee, 2007, published in Izvestiya Akademii Nauk, Seriya Biologicheskaya, 2007, No. 1, pp. 35–44.

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Krylatov, A.V., Maslov, L.N., Ermakov, S.Y. et al. Significance of cardiac cannabinoid receptors in regulation of cardiac rhythm, myocardial contractility, and electrophysiologic processes in heart. Biol Bull Russ Acad Sci 34, 28–35 (2007). https://doi.org/10.1134/S1062359007010049

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  • DOI: https://doi.org/10.1134/S1062359007010049

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