Heijnis J B, van Zwieten P A
Department of Pharmacotherapy, Academic Medical Center, University of Amsterdam, The Netherlands.
Pharmacology. 1993 Apr;46(4):193-7. doi: 10.1159/000139045.
The effects of nifedipine, verapamil and diltiazem on K(+)-induced contraction were investigated in isolated aortic rings from diabetic and age-matched control rats. Six weeks after streptozotocin injection there was no significant difference between the maximum isometric contraction to KCl (80 mmol/l), when expressed per milligram tissue weight, in aortic rings from diabetic rats and those from controls. A concentration-dependent inhibition of the K(+)-induced contraction was observed for the three Ca antagonists in aortic rings from both diabetic and age-matched control rats. Notably, the K(+)-induced contraction in aortic preparations from diabetic rats was more sensitive to nifedipine compared to control preparations (pD2: 8.61 vs. 8.31, p < 0.05), while no significant change in sensitivity towards verapamil (pD2: 6.99 vs. 6.92, p > 0.05) or diltiazem (pD2: 6.33 vs. 6.28, p > 0.05) could be demonstrated. Our data indicate a greater interference of nifedipine with voltage-operated channels in diabetic aortas compared with controls. Since a similar antispasmodic activity was found for diltiazem and verapamil it might be specific for dihydropyridine Ca antagonists.
在糖尿病大鼠和年龄匹配的对照大鼠的离体主动脉环中,研究了硝苯地平、维拉帕米和地尔硫䓬对钾离子诱导收缩的影响。链脲佐菌素注射六周后,按每毫克组织重量计算,糖尿病大鼠主动脉环和对照大鼠主动脉环对氯化钾(80毫摩尔/升)的最大等长收缩之间无显著差异。在糖尿病大鼠和年龄匹配的对照大鼠的主动脉环中,观察到三种钙拮抗剂对钾离子诱导的收缩具有浓度依赖性抑制作用。值得注意的是,与对照制剂相比,糖尿病大鼠主动脉制剂中钾离子诱导的收缩对硝苯地平更敏感(亲和力常数的负对数:8.61对8.31,p<0.05),而对维拉帕米(亲和力常数的负对数:6.99对6.92,p>0.05)或地尔硫䓬(亲和力常数的负对数:6.33对6.28,p>0.05)的敏感性无显著变化。我们的数据表明,与对照相比,硝苯地平对糖尿病主动脉中电压门控通道的干扰更大。由于地尔硫䓬和维拉帕米具有相似的解痉活性,这种作用可能是二氢吡啶类钙拮抗剂所特有的。