Summary
The chronotropic effect of Bay K 8644, a dihydropyridine known to increase the slow inward current, was studied in spontaneously beating rat atria. Increases in atrial rate were concentration-dependent and the maximal increase (106 ± 10 beats/min) was obtained at 3 × 10−6 mol/l. Reserpine pretreatment, or propranolol 3 × 10−7 mol/l, or propranolol plus prazosin 10−6 mol/l decreased the maximum chronotropic effect of Bay K 8644 by about 60%. Blockade of the removal mechanisms of catecholamines (hydrocortisone 3 × 10−5 mol/l plus cocaine 10−5 mol/1) did not prevent the chronotropic effect of the compound. Exposure to Bay K 8644 increased the spontaneous outflow of tritium from atria preloaded with [3H]-norepinephrine by 30%. The results indicate that Bay K 8644 produces positive chronotropic effects through two mechanisms: a direct one and an indirect mechanism that involves the participation of norepinephrine released from sympathetic nerve endings.
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de Hurtado Camilion, M.C., Gende, O.A. & Cingolani, H.E. Positive chronotropic effect of Bay K 8644: participation of endogenous norepinephrine. Naunyn-Schmiedeberg's Arch Pharmacol 340, 452–455 (1989). https://doi.org/10.1007/BF00167048
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DOI: https://doi.org/10.1007/BF00167048