de Hurtado M C, Gende O A, Cingolani H E
Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Medicas Universidad Nacional de La Plata, Argentina.
Naunyn Schmiedebergs Arch Pharmacol. 1989 Oct;340(4):452-5. doi: 10.1007/BF00167048.
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.
已知二氢吡啶类化合物Bay K 8644可增强慢内向电流，本研究观察了其对大鼠离体心房自律性的影响。Bay K 8644对心房率的增加呈浓度依赖性，在3×10(-6)mol/L时可使心率最大增加(106±10次/分)。利血平预处理、3×10(-7)mol/L普萘洛尔或3×10(-7)mol/L普萘洛尔加10(-6)mol/L哌唑嗪可使Bay K 8644的最大变时作用降低约60%。阻断儿茶酚胺的摄取机制(3×10(-5)mol/L氢化可的松加10(-5)mol/L可卡因)并不影响该化合物的变时作用。用Bay K 8644处理预先装载[3H] - 去甲肾上腺素的心房，可使[3H] - 去甲肾上腺素的自发释放增加30%。结果表明，Bay K 8644通过两种机制产生正性变时作用：一种是直接作用，另一种是间接作用，后者涉及交感神经末梢释放的去甲肾上腺素的参与。
