Use of cultured atherosclerotic cells for investigation of antiatherosclerotic effects of anipamil and other calcium antagonists.
Calcium antagonists have been shown to exhibit an antiatherosclerotic action in primary cultures of human aortic atherosclerotic cells by causing a reduction in intracellular lipid content, proliferative activity and synthesis of the extracellular matrix. Verapamil and nifedipine exhibited the highest efficacy in this respect. The new calcium antagonist, anipamil (racemate and enantiomers), has been tested in cell cultures. At 10(-6) M and higher concentrations, anipamil and its enantiomers produced considerable decrease in intracellular content 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 and greater than that of nifedipine. Plasma obtained from patients after administration of 80 mg verapamil or 20 mg nifedipine significantly lowered the cholesterol content of cultured cells. Blood plasma of most atherosclerotic patients possesses atherogenic properties, i.e., it is able to increase the cholesterol content in cultured cells. Plasma atherogenicity seen in cultures decreased considerably or even disappeared after both nifedipine and verapamil administration. After 28 days of nifedipine therapy, plasma atherogenicity 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 optimisation of direct antiatherogenic and antiatherosclerotic therapy.
Orekhov
A N
AN
USSR Cardiology Research Centre, Moscow, Russia.
Tertov
V V
VV
Lyakishev
A A
AA
Ruda MYa
D001011:Aorta / Q000187:drug effects / Q000473:pathology; D001161:Arteriosclerosis / Q000188:drug therapy / Q000473:pathology*; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002784:Cholesterol / Q000032:analysis; D004730:Endothelium, Vascular / Q000737:chemistry / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D008055:Lipids / Q000032:analysis; D009543:Nifedipine / Q000494:pharmacology* / Q000627:therapeutic use; D011437:Propylamines / Q000494:pharmacology* / Q000627:therapeutic use; D014700:Verapamil / Q000494:pharmacology* / Q000627:therapeutic use
D002121:Calcium Channel Blockers; D008055:Lipids; D011437:Propylamines; D002784:Cholesterol; C045313:anipamil; D014700:Verapamil; D009543:Nifedipine