Positive chronotropic effect of Bay K 8644: participation of endogenous norepinephrine.
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 x 10(-6) mol/l. Reserpine pretreatment, or propranolol 3 x 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 x 10(-5) mol/l plus cocaine 10(-5) mol/l) 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.
de Hurtado
M C
MC
Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Medicas Universidad Nacional de La Plata, Argentina.
Gende
O A
OA
Cingolani
H E
HE
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism / Q000502:physiology*; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D012110:Reserpine / Q000494:pharmacology
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D012110:Reserpine; D011433:Propranolol; D009638:Norepinephrine; D011224:Prazosin