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.
Cristofori
P
P
Glaxo Research Laboratories, Glaxo SpA, Verona, Italy.
Terron
A
A
Micheli
D
D
Bertolini
G
G
Gaviraghi
G
G
Carpi
C
C
D000284:Administration, Oral; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000098:blood supply / Q000473:pathology; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D004095:Dihydropyridines / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D005654:Fundus Oculi; D006974:Hypertension, Malignant / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009206:Myocardium / Q000473:pathology; D009929:Organ Size; D051381:Rats; D011918:Rats, Inbred SHR; D012982:Sodium, Dietary / Q000008:administration & dosage
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D012982:Sodium, Dietary; C060285:lacidipine