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Effects of Calcium Channel Blockers on Cultured Rat Embryos

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 μg 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 μg 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.