Takayama S, Furukawa Y, Murakami M, Chiba S
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto, Japan.
Jpn J Pharmacol. 1994 Sep;66(1):115-22. doi: 10.1254/jjp.66.115.
We investigated whether pinacidil, a K+ATP channel opener like acetylcholine and adenosine, attenuated the positive chronotropic and inotropic responses to norepinephrine in isolated, blood-perfused dog atrial and ventricular preparations. Pinacidil (0.01-0.3 mumol) decreased atrial and ventricular contractile force to a much greater extent than sinus rate in a dose-related manner. Pinacidil dose-dependently attenuated increases in atrial and ventricular forces induced by norepinephrine but not increases in sinus rate. Pinacidil similarly attenuated the positive atrial and ventricular inotropic responses to Bay k 8644 and CaCl2. The pinacidil doses producing a fifty percent decrease (ED50) of the atrial and ventricular contractile force were not significantly different from the respective pinacidil doses producing a fifty percent inhibition (ID50) of the positive inotropic responses to norepinephrine, Bay k 8644 and CaCl2. Ouabain (5 and 15 nmol) did not affect the decreases in atrial and ventricular contractile force in response to pinacidil. These results suggest that the K+ATP-channel activator pinacidil, unlike acetylcholine or adenosine, functionally attenuates increases in ventricular and atrial contractile force in the responses to norepinephrine and other cardiotonics due to shortening of the action potential duration induced by K+ATP-channel activation in the dog heart.
我们研究了吡那地尔（一种与乙酰胆碱和腺苷类似的K⁺ATP通道开放剂）是否能减弱去甲肾上腺素对离体、血液灌注的犬心房和心室标本产生的正性变时和变力反应。吡那地尔（0.01 - 0.3 μmol）以剂量相关的方式使心房和心室收缩力的降低程度远大于窦性心率的降低程度。吡那地尔剂量依赖性地减弱去甲肾上腺素诱导的心房和心室力的增加，但不减弱窦性心率的增加。吡那地尔同样减弱了对Bay k 8644和氯化钙的正性心房和心室变力反应。使心房和心室收缩力降低50%（ED50）的吡那地尔剂量与使对去甲肾上腺素、Bay k 8644和氯化钙的正性变力反应抑制50%（ID50）的各自吡那地尔剂量无显著差异。哇巴因（5和15 nmol）不影响吡那地尔引起的心房和心室收缩力的降低。这些结果表明，与乙酰胆碱或腺苷不同，K⁺ATP通道激活剂吡那地尔在功能上减弱了犬心脏中因K⁺ATP通道激活诱导的动作电位时程缩短而导致的对去甲肾上腺素和其他强心剂反应中心房和心室收缩力的增加。
