[Sex and age differences in the effect of verapamil on rat cardiac function]

The author reports that a relatively high dose of verapamil produces sex-related cardiac effects, especially on the conducting system in adult rats. A single dose of verapamil (0.5-1 mg/kg, i.v.) caused a marked AV block and a reduction in heart rate to 50-60% in adult males, but not in females. There was no sex difference in the hypotensive effect of verapamil. At 3, 5 or 7 weeks of age, verapamil (1 mg/kg, i.v.) induced a 10-20% reduction of the heart rate without AV block in both male and female rats. In 8-week-old male rats, the reduction in the heart rate became apparent, and AV block appeared following a single i.v. injection of verapamil. The adult pattern in cardiac response to verapamil was observed at 11 weeks of age and afterward. Castration in adult male and female rats resulted in an intermediate pattern of the response to verapamil in intact male and female rats. Acute treatment with testosterone (20 mg/kg, s.c.) in castrated male and female rats induced a decrease in the basal heart rate and increased the cardiac responsiveness to verapamil in castrated female rats. Estradiol-17 beta failed to alter the responsiveness of castrated rats to verapamil. These results suggest that testosterone may play a role in the sex difference of the cardiac responses to verapamil in rats.