Vascular Protection of Lacidipine in Salt-Loaded Dahl-S Rats at Nonsustained Antihypertensive Doses

The aim of this study was to characterize the antihypertensive and vasoprotective properties of lacidipine in salt-loaded Dahl-S rats, a suitable animal model of malignant hypertension. After 9 weeks of a high (8%) sodium chloride (NaCl) diet, 80% of the untreated Dahl-S rats died (20% survival rate) whereas a 100% survival rate was observed with chronic treatment with lacidipine at doses of 0.1 (equivalent to the recommended dose in humans), 0.3, 1, and 10 mg/kg once daily by gastric gavage. The most interesting results included the following: (a) Only the highest dose tested (10 mg/kg once daily) was able to control the increase in blood pressure, which was measured 24 h after the preceding administration of drug, yet a 100% survival rate was maintained. (b) There appeared to be prevention of brain lesions, which is very likely the cause of the survival of all of the lacidipine-treated rats in this study. (c) A clear dose-related vascular protection was observed in other tissues. In conclusion, lacidipine protects against the vascular damage and concomitant increase in mortality of salt-loaded Dahl-S rats even at doses that do not adequately control the development of hypertension.