De Jong J W, Harmsen E, De Tombe P P, Keijzer E
Eur J Pharmacol. 1982 Jun 16;81(1):89-96. doi: 10.1016/0014-2999(82)90604-5.
An ATP-sparing effect has been demonstrated for a number of calcium antagonists. Nifedipine probably has a similar action, but data supporting this view are limited. Therefore we decided to study the effect of nifedipine on high-energy phosphate (and carbohydrate) metabolism in the ischemic rat heart. Langendorff preparations were made ischemic for less than 15 min. The reduction in coronary flow was 60 or 70%. Apex displacement during ischemia, a measure of contractility, was comparable for nifedipine-treated and untreated hearts. Ischemia caused a considerable release of the AMP catabolites adenosine, inosine and (hypo)xanthine, and of lactate. Nifedipine (10-100 micrograms/l) prevented this in a dose-dependent way. The highest dose reduced the release of purines and lactate by 90% (P less than 0.01) and 60% (P less than 0.001), respectively. The drug acted in a similar way during reperfusion. Due to ischemia, the adenylate energy charge (ATP + 0.5 ADP)/(ATP + ADP + AMP), decreased 15% (P less than 0.001); nifedipine at a concentration of 100 micrograms/l prevented this decrease (P less than 0.05). We conclude that nifedipine exerts a beneficial effect on myocardial adenine nucleotide metabolism during ischemia and reperfusion.
已证实多种钙拮抗剂具有节省三磷酸腺苷（ATP）的作用。硝苯地平可能也有类似作用，但支持这一观点的数据有限。因此，我们决定研究硝苯地平对缺血大鼠心脏高能磷酸（及碳水化合物）代谢的影响。制备Langendorff标本使其缺血不到15分钟。冠状动脉血流减少60%或70%。缺血期间的心尖位移（一种收缩性指标）在硝苯地平处理组和未处理组心脏中相当。缺血导致大量释放AMP分解代谢产物腺苷、肌苷和（次）黄嘌呤以及乳酸。硝苯地平（10 - 100微克/升）以剂量依赖方式阻止了这种情况。最高剂量分别使嘌呤和乳酸的释放减少90%（P < 0.01）和60%（P < 0.001）。该药物在再灌注期间也有类似作用。由于缺血，腺苷酸能荷（ATP + 0.5 ADP）/（ATP + ADP + AMP）降低了15%（P < 0.001）；100微克/升浓度的硝苯地平阻止了这种降低（P < 0.05）。我们得出结论，硝苯地平在缺血和再灌注期间对心肌腺嘌呤核苷酸代谢发挥有益作用。
