Briscoe M G, Smith H J
Cardiovasc Res. 1982 Apr;16(4):173-7. doi: 10.1093/cvr/16.4.173.
The effects of acidosis on the myocardial sensitivity to verapamil and nifedipine were examined by measuring the changes in tension in cat papillary muscles perfused in oxygenated physiological saline. Calcium concentration was altered over a range of 2 to 12 mmol . litre-1 and pH adjusted to 7.4, 6.8 or 6.0. Addition of verapamil or nifedipine moved the calcium dose response to the right. At pH 7.4 a Schild plot confirmed competitive interaction between verapamil and calcium, with a calculated dissociation constant (KB) for verapamil of 4.6 +/- 0.2 micrograms . cm-3. At pH 6.0 the slope was less than 1.0 (not significant, P = 0.2) but KB was significantly lower (P less than 0.01) at 0.62 +/- 0.4 microgram . cm-3. Similar enhancement of sensitivity by lowered pH was found for nifedipine. It is proposed that partial inhibition of the slow channel by acidosis increases the sensitivity to calcium entry blockers. This might create a differential effect between normal and diseased tissue in vivo.
通过测量在含氧生理盐水中灌注的猫乳头肌的张力变化，研究了酸中毒对心肌对维拉帕米和硝苯地平敏感性的影响。钙浓度在2至12 mmol·升-1范围内变化，pH值调节至7.4、6.8或6.0。加入维拉帕米或硝苯地平使钙剂量反应向右移动。在pH 7.4时，Schild图证实维拉帕米与钙之间存在竞争性相互作用，计算出维拉帕米的解离常数（KB）为4.6±0.2微克·厘米-3。在pH 6.0时，斜率小于1.0（无显著性差异，P = 0.2），但KB显著降低（P＜0.01），为0.62±0.4微克·厘米-3。对于硝苯地平，也发现降低pH会类似地增强敏感性。有人提出，酸中毒对慢通道的部分抑制会增加对钙通道阻滞剂的敏感性。这可能会在体内正常组织和患病组织之间产生差异效应。
