Antiatherogenic properties of calcium channel blockers

Abstract

Human atherosclerotic disease is characterized by focal accumulation of lipids, fibrous matrix materials, and calcium over several decades of life. A major difficulty in determining the efficacy of antiatherogenic agents has been the lack of appropriate animal models that reproducibly mimic the human arterial lesion. Studies in cholesterol-fed rabbits have become the “universal” model for testing therapeutic agents. Despite the difficulties in obtaining reproducible results with this animal model system, it is well-documented that high doses of calcium channel blockers can significantly reduce the accumulation of cholesterol and lipid in the aortas of cholesterol-fed rabbits. Isradipine is the only calcium channel blocker that has been shown to inhibit arterial cholesterol accumulation in the rabbit model at doses that approximate the human dose range. A dietary modification of the standard cholesterol-feeding regimen may provide an improved animal model for studies in atherogenic lesion proliferation. Such animal model experiments have provided the basis for the first prospective trials on the progression of human coronary artery disease using long-term administration of calcium channel blockers.