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-mu-g kg-1) with the appearance of second-degree A-V blocks at 300-mu-g kg-1. A slight decrease in contractile index (CI) was detected only at the highest dose used, 300-mu-g kg-1. The other dihydropyridine, amlodipine, showed a lower degree of vasodilatory activity (ED25% = 330-mu-g kg-1), appearance of second-degree A-V blocks starting from 1,000-mu-g kg-1 and a pronounced decrease in CI at 3,000-mu-g kg-1. Verapamil and diltiazen produced dose-related decreases in blood pressure (ED25% = 32 and 175-mu-g kg-1, respectively) and appearance of second-degree A-V blocks at 300 and 1,000-mu-g 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.