Ban Y, Nakatsuka T, Matsumoto H
Development Research Laboratories, Banyu Pharmaceutical Co., Ltd., Saitama, Japan.
J Appl Toxicol. 1996 Mar-Apr;16(2):147-51. doi: 10.1002/(SICI)1099-1263(199603)16:2<147::AID-JAT324>3.0.CO;2-L.
Gestational day 11 rat embryos were cultured for 20 h in the presence of nifedipine (NIF), diltiazem (DIL) and verapamil (VER), and the effects of these calcium channel blockers on embryonic heart rate and gross morphology were examined. Reductions of embryonic heart rate were dose dependent and reversible. Effects on the heart rate were seen at doses as low as 0.3, 1 and 20 micrograms ml-1 for VER, DIL and NIF, respectively. Retardation of embryonic growth and morphological abnormalities, which were related to circulation defects, were seen at termination. The minimum doses to produce 100% effect on gross morphology were 2, 6 and 40 micrograms ml-1 for VER, DIL and NIF, respectively. These findings suggest that embryolethality seen in vivo studies is partly due to circulation defects and the associated morphological abnormalities in rats.
妊娠第11天的大鼠胚胎在硝苯地平（NIF）、地尔硫䓬（DIL）和维拉帕米（VER）存在的情况下培养20小时，研究了这些钙通道阻滞剂对胚胎心率和总体形态的影响。胚胎心率的降低呈剂量依赖性且可逆。VER、DIL和NIF分别在低至0.3、1和20微克/毫升的剂量下即可观察到对心率的影响。在实验结束时观察到胚胎生长迟缓和形态异常，这些异常与循环缺陷有关。VER、DIL和NIF对总体形态产生100%影响的最小剂量分别为2、6和40微克/毫升。这些发现表明，体内研究中观察到的胚胎致死率部分归因于大鼠的循环缺陷及相关的形态异常。
