Abstract
Previous studies have shown that calcium channel blockers may reduce the development of experimental atherosclerosis, and that nifedipine may slow the progression of coronary atherosclerosis in humans. The mechanisms responsible for this antiatherogenic effect are still unclear. It has been recently proposed that oxygen free radicals can induce the oxidation of human low-density lipoproteins (LDL) and that oxidized LDL may be an atherogenic stimulus. Previous studies in other systems have shown that calcium channel blockers may effectively inhibit oxygen radical-induced lipid peroxidation in vitro. Thus, the aim of the present study was to investigate whether calcium channel blockers may also reduce LDL modifications induced by oxygen radicals. Isolated human LDL were exposed to oxygen radicals generated by CuSO4 (10 μM for 18 hours) after a 30 minute preincubation with different concentrations (1-100 μM) of nifedipine, diltiazem, and verapamil. Lipid peroxidation was measured from malonyldihaldehyde (MDA) production. Oxygen radical-induced damage on apolipoprotein-B100 was evaluated by acrylamide and agarose gel electrophoresis. Calcium channel blockers dose-dependently prevented oxidation of both the lipid and protein components of LDL. MDA formation was reduced in LDL pre-incubated with calcium antagonists before exposure to oxygen radicals (% MDA inhibition was 89.8 ± 6.9 with 30 μM nifedipine, 68.6 ± 4.9 with 30 μM verapamil, and 68.6 ± 7.1 with 30 μM diltiazem; p <0.01 vs. controls). Similarly, apolipoprotein-B100 integrity was preserved against oxygen radical attack in the presence of calcium antagonists. Thus, calcium channel blockers reduce the oxidation of human LDL in vitro. These data suggest that reduced formation of atherogenic oxidized LDL may be an additional mechanism for the antiatherosclerotic effects of calcium channel blockers in vivo.
Original language | English |
---|---|
Pages (from-to) | 417-424 |
Number of pages | 8 |
Journal | Cardiovascular Drugs and Therapy |
Volume | 10 |
Issue number | 4 |
DOIs | |
Publication status | Published - 1996 |
Keywords
- Atherosclerosis
- Calcium channel-blockers
- Low density lipoprotein
- Oxygen radicals
- Peroxidation
ASJC Scopus subject areas
- Pharmacology (medical)
- Cardiology and Cardiovascular Medicine
- Pharmacology