title: Protective effects of calcium channel blockers against free radical-impaired endothelial cell proliferation.
abstract: We have shown previously that the lipophilic calcium channel blockers exhibit membrane antioxidant activity. In the present study, when attached bovine aortic endothelial cells were exposed for 20 min to a low concentration of oxy-radicals generated from dihydroxyfumarate + Fe-ADP, no loss of glutathione or viability was detected; however, cell number, determined 48 hr later by the tetrazolium salt MTT assay, decreased to 45% of controls. Treatment of the cells for 1 hr with the calcium blockers (2-20 microM) prior to free radical exposure protected against the impaired cell growth in a concentration-dependent manner. The order of potency was nicardipine > or = nifedipine > or = verapamil > diltiazem, which appears to parallel their antioxidant potency. In addition, (+)-nicardipine, and its pharmacologically inactive isomer, (-)-nicardipine, were similarly effective. We conclude that it was the antioxidant activity of the calcium channel blockers that preserved the cell growth capacity against free-radical damage; such protective effects may contribute to their antiatherogenic effects.
authors.affiliation: Department of Medicine, George Washington University Medical Center, Washington, DC 20037, USA.
authors.forename: I T
authors.initials: IT
authors.lastname: Mak
authors.forename: P
authors.initials: P
authors.lastname: Boehme
authors.forename: W B
authors.initials: WB
authors.lastname: Weglicki
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003124:Colorimetry; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D009529:Nicardipine / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000633:toxicity*; D013237:Stereoisomerism; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D000975:Antioxidants; D002121:Calcium Channel Blockers; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; D013844:Thiazoles; D009529:Nicardipine; C022616:thiazolyl blue