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.Centro de Investigaciones Cardiovasculares