Protective effects of calcium channel blockers against free radical-impaired endothelial cell proliferation.

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.