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 atta ched bovine aortic endothelial cells were exposed for 20 min to a low concentration of oxy-radicals generated from dihydroxyfumarate + Fe-AD P, no loss of glutathione or viability was detected; however, cell num ber, determined 48 hr later by the tetrazolium salt MTT assay, decreas ed to 45% of controls. Treatment of the cells for 1 hr with the calciu m blockers (2-20 mu M) prior to free radical exposure protected agains t the impaired cell growth in a concentration-dependent manner. The or der of potency was nicardipine greater than or equal to nifedipine gre ater than or equal to verapamil > diltiazem, which appears to parallel their antioxidant potency. In addition, (+)-nicardipine, and its phar macologically inactive isomer, (-)-nicardipine, were similarly effecti ve. We conclude that it was the antioxidant activity of the calcium ch annel blockers that preserved the cell growth capacity against free-ra dical damage; such protective effects may contribute to their antiathe rogenic effects.