DIFFERENTIAL MEMBRANE INTERACTIONS OF CALCIUM-CHANNEL BLOCKERS - IMPLICATIONS FOR ANTIOXIDANT ACTIVITY

Lipid peroxidation causes cellular damage during aging and various dis eases, including atherosclerosis. Chronic administration of highly lip ophilic calcium channel blockers (CCB) may reduce lipid peroxidation a s a result of concentration in cell membranes and altering physico-che mical properties of the lipid bilayer. In this study, small angle X-ra y scattering was used to examine reconstituted cardiac membrane lipid bilayers in the presence of CCB with various antioxidant activities, i ncluding nisoldipine, nifedipine, and diltiazem. Analysis of one-dimen sional electron density profiles demonstrated that these compounds hav e different molecular distributions relative to the center of the memb rane: diltiazem (+/- 14-22 Angstrom), nifedipine (+/- 12-22 Angstrom), and nisoldipine (+/- 7-22 Angstrom). The overall hydrocarbon core wid th for control samples was 44 Angstrom and was unaffected by the addit ion of drugs at these concentrations (< 1% by mass). High resolution d ifferential scanning calorimetry indicated that CCB markedly perturbed the thermotropic properties of liposomes, including thermal phase tra nsition temperature and enthalpy, relative to control samples. The eff ects of these compounds on membrane thermotropic properties correlate with their reported antioxidant activities. These data support the hyp othesis that calcium channel blockers have potent physico-chemical int eractions with the membrane lipid bilayer, which may underlie their an tioxidant activity.