Antiatherosclerotic effects of anipamil, verapamil and other calcium antagonists studied on cell culture

Abstract

Calcium antagonists exhibit direct antiatherosclerotic action in primary culture of human aortic atherosclerotic cells by lowering intracellular lipid content, proliferative activity and synthesis of the extracellular matrix. Verapamil exhibited the highest efficacy in this respect. New calcium antagonist, anipamil, and its enantiomers have been tested in cell culture. At 10-6 M and higher concentrations, anipamil and its enantiomers produced considerable decrease in intracellular contents of cholesteryl esters, triglycerides and free cholesterol, suppressed cell proliferation and inhibited synthesis of the extracellular matrix. The efficacy of anipamil enantiomers and racemate was similar to that of verapamil. Blood plasma obtained from patients after administration of 80 mg verapamil or 20 mg nifedipin significantly lowered the cholesterol content of cultured cells. Blood plasma of most atherosclerotic patients possesses atherogenic properties, i.e. it is able to increase cholesterol content in cultured cells. Plasma atherogenicity manifested in culture decreased considerably or even disappeared after both nifedipine and verapamil administration. After 28 days of nifedipine therapy, plasma atherogenenicity was lower compared with the initial value at the beginning of the treatment. These observations suggest that control of plasma atherogenicity after drug administration may provide an additional tool for optimization of direct antiatherogenic and antiatherosclerotic therapy.