Lacidipine: experimental evidence of vasculoprotective properties.
Lacidipine is a second-generation 1,4-dihydropyridine calcium antagonist, whose potent and long-lasting antihypertensive properties prompted us to investigate whether its chronic administration to Dahl-S rats prevented salt-induced hypertension, vasculopathy, and accelerated mortality. These studies revealed that lacidipine proved vasoprotective when administered both prophylactically and therapeutically at doses of 0.1 and 0.3 mg/kg p.o. once a day, largely equivalent to the therapeutic doses. A generalized dose-related protection against necrotizing vasculopathy and brain damage was detected, although only the highest dose used (10 mg/kg) controlled the development of hypertension. These protective properties were further confirmed in stroke-prone spontaneously hypertensive rats, which develop accelerated mortality as a result of salt-induced cerebral apoplexy and renal lesions. All untreated controls died within 12 weeks of salt-rich diet, whereas all animals survived during the same period when treated prophylactically with lacidipine at 0.3 and 1 mg/kg p.o. once a day, although a slight reduction in systolic blood pressure was measured only with the highest dose. No cerebral lesions and a clear protection against renal damage were detected in lacidipine-treated animals. In conclusion, these findings reinforce the concept that the beneficial effects of calcium antagonists are not simply restricted to a reduction in blood pressure.
Cristofori
P
P
Glaxo Research Laboratories, Glaxo S.p.A., Verona, Italy.
Micheli
D
D
Terron
A
A
Gaviraghi
G
G
D000818:Animals; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D003900:Desoxycorticosterone; D004095:Dihydropyridines / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D007668:Kidney / Q000473:pathology; D011507:Proteinuria / Q000188:drug therapy; D051381:Rats; D011919:Rats, Inbred Strains
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C060285:lacidipine; D003900:Desoxycorticosterone