A comparative study on the vascular selectivity of lacidipine in the pithed rat

This paper describes the results of a series of experiments in pithed rat, infused with angiotensin II, in order to characterize better vascular selectivity of lacidipine in comparison with other calcium entry blockers, namely amlodipine, verapamil and diltiazem. Lacidipine induced dose-related decreases in blood pressure (ED25% for mean blood pressure = 6 micrograms kg-1) with the appearance of second-degree A-V blocks at 300 micrograms kg-1. A slight decrease in contractile index (CI) was detected only at the highest dose used, 300 micrograms kg-1. The other dihydropyridine, amlodipine, showed a lower degree of vasodilatory activity (ED25% = 330 micrograms kg-1), appearance of second-degree A-V blocks starting from 1,000 micrograms kg-1 and a pronounced decrease in CI at 3,000 micrograms kg-1. Verapamil and diltiazem produced dose-related decreases in blood pressure (ED25% = 32 and 175 micrograms kg-1, respectively) and appearance of second-degree A-V blocks at 300 and 1,000 micrograms kg-1, respectively. Pronounced decreases in CI were detected with verapamil whereas diltiazem induced a more specific negative chronotropic effect. In conclusion, these results confirmed the marked vascular selectivity of lacidipine and give further evidence that this drug may be a suitable agent for the treatment of hypertension.