Department of Pharmacology, Faculty of Medicine, University of Hong Kong, 5 Sassoon Road, Hong Kong, Hong Kong China.
Environ Toxicol Pharmacol. 1996 May 15;1(3):207-12. doi: 10.1016/1382-6689(96)00013-0.
We have previously shown that pH changes alter the cardiovascular responses to verapamil in rat, in vivo and in isolated rat heart. The current study investigated the influence of pH changes on the actions of verapamil on potassium- or noradrenaline-stimulated contraction in rat tail arteries. The proximal 2-2.5 cm of ventral tail artery was bathed in and perfused initially (20-25 min) with physiological salt solution (pH 7.4) which was later made calcium-free at pH 7.4 (control), pH 7.2 (acidosis) or pH 7.67 (alkalosis). After equilibration each artery was exposed to verapamil following which the contractile responses to increasing concentrations of calcium were recorded. The patterns of responses in noradrenaline- or potassium-stimulated arteries were different. In normal conditions, the vasodilator effect of verapamil was predominant in potassium-stimulated arteries but less in the noradrenaline-stimulated preparations. With pH changes the effect of verapamil was enhanced more in noradrenaline- than in potassium-stimulated arteries. It is postulated that pathology-induced changes in the character of calcium channels could alter the effect of calcium channel blockers.
我们之前已经表明，pH 值的变化会改变体内和离体大鼠心脏中维拉帕米对心血管的反应。本研究调查了 pH 值变化对维拉帕米对大鼠尾动脉中钾或去甲肾上腺素刺激收缩作用的影响。腹侧尾动脉的近端 2-2.5cm 最初用生理盐水（pH 7.4）灌流和灌注（20-25 分钟），随后在 pH 7.4（对照）、pH 7.2（酸中毒）或 pH 7.67（碱中毒）时使钙离子自由。在平衡后，每条动脉都暴露于维拉帕米，然后记录对增加浓度的钙的收缩反应。去甲肾上腺素或钾刺激的动脉中的反应模式不同。在正常情况下，维拉帕米在钾刺激的动脉中表现出更强的血管扩张作用，但在去甲肾上腺素刺激的制剂中作用较小。随着 pH 值的变化，维拉帕米在去甲肾上腺素刺激的动脉中的作用比在钾刺激的动脉中增强得更多。据推测，病理诱导的钙通道特性变化可能会改变钙通道阻滞剂的作用。
