TY - JOUR
T1 - Positive chronotropic effect of Bay K 8644
T2 - participation of endogenous norepinephrine
AU - de Hurtado Camilion, Maria C.
AU - Gende, Oscar A.
AU - Cingolani, Horacio E.
PY - 1989/10
Y1 - 1989/10
N2 - 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.
AB - 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.
KW - Bay K 8644
KW - Chronotropic response
KW - Norepinephrine release
KW - Rat atria
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U2 - 10.1007/BF00167048
DO - 10.1007/BF00167048
M3 - Article
C2 - 2479845
AN - SCOPUS:0024468114
SN - 0028-1298
VL - 340
SP - 452
EP - 455
JO - Naunyn-Schmiedeberg's Archives of Pharmacology
JF - Naunyn-Schmiedeberg's Archives of Pharmacology
IS - 4
ER -