The antiatherogenic effects of amlodipine: promise of preclinical data.
Atherosclerosis is a complex and multifactorial disease, the endpoint of which is the formation of a calcified plaque. Intermediate events include intimal injury, smooth muscle cell proliferation and migration, macrophage infiltration, lipid accumulation and excess formation of ground substance. To determine whether the newly developed, long-acting calcium antagonist, amlodipine, slows the development of atherosclerotic lesions under experimental conditions, young New Zealand white rabbits were fed on a diet of 2% cholesterol plus 1% peanut oil for up to 12 weeks. Half the rabbits received 1 or 5 mg amlodipine/kg body weight/day. Amlodipine caused a significant and dose-dependent reduction in lesion formation in the thoracic aorta. At the same time thoracic aorta Ca2+ and cholesterol content were maintained at near normal levels, despite the raised plasma cholesterol levels. The protective effect of amlodipine persisted throughout a treatment period of 12 weeks, indicating the absence of tachyphylaxis.
Nayler
W G
WG
Department of Medicine, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia.
D017311:Amlodipine / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000737:chemistry / Q000473:pathology; D001161:Arteriosclerosis / Q000378:metabolism / Q000517:prevention & control*; D002118:Calcium / Q000032:analysis / Q000378:metabolism; D002784:Cholesterol / Q000032:analysis / Q000097:blood / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D011817:Rabbits; D013194:Staining and Labeling; D013997:Time Factors
D017311:Amlodipine; D002784:Cholesterol; D002118:Calcium