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Effects of Ca-antagonists on oxidative susceptibility of low density lipoprotein (LDL)
H Yoshida1, M Ayaori, M Suzukawa
1First Department of Internal Medicine, National Defense Medical College, Tokorozawa, Japan.
Insights
The calcium channel blocker nilvadipine, but not amlodipine, inhibited LDL oxidation in hypertensive patients. This suggests lipophilic calcium antagonists may help prevent atherosclerosis.
Area of Science:
- Cardiovascular Pharmacology
- Oxidative Stress Research
- Atherosclerosis Pathogenesis
Background:
- Essential hypertension is a major risk factor for atherosclerosis.
- Oxidative modification of low-density lipoprotein (LDL) plays a crucial role in atherogenesis.
- Calcium channel blockers (Ca-antagonists) are widely used to manage hypertension.
Purpose of the Study:
- To investigate the effect of nilvadipine, a lipophilic Ca-antagonist, on LDL oxidation in patients with essential hypertension.
- To compare the effects of nilvadipine and amlodipine, a hydrophilic Ca-antagonist, on LDL oxidative modification.
- To explore the potential of Ca-antagonists in preventing atherosclerosis.
Main Methods:
- Twelve adults with essential hypertension were treated with nilvadipine (4 mg b.i.d.) for 4 weeks.
- LDL samples were isolated at baseline (week 0) and end of treatment (week 4).
- LDL oxidation was assessed by measuring conjugated diene formation, lag time, thiobarbituric acid reactive substances (TBARS), and agarose electrophoretic mobility.
Main Results:
- Nilvadipine treatment significantly prolonged the lag time of LDL oxidation by 12.6% (p < 0.05).
- In vitro studies showed nilvadipine inhibited LDL oxidative modification, while amlodipine did not.
- No significant differences were observed in lipid levels, LDL composition, or antioxidant levels between weeks 0 and 4.
Conclusions:
- The lipophilic Ca-antagonist nilvadipine demonstrates inhibitory effects on LDL oxidation.
- The observed effect on LDL oxidation is dependent on the lipophilicity of the Ca-antagonist.
- These findings suggest a potential role for lipophilic Ca-antagonists in the prevention of atherosclerosis.
Abstract:
Twelve adults (age 32-61 years) with essential hypertension were recruited from the outpatient clinics of National Defense Medical College hospital to serve as subjects in the present study. They were treated with nilvadipine, a Ca-antagonist, 4 mg b.i.d. for 4 weeks. LDL samples were isolated by ultracentrifugation at the beginning (week 0) and at the end (week 4) of the treatment regimen. The formation of conjugated dienes was measured by incubating 100 micrograms of LDL protein with 2 mumol CuSO4 in 2 ml phosphate buffered saline (PBS). There were no significant differences between lipids levels, composition and anti-oxidant levels of LDL at weeks 0 and 4. The lag time of LDL oxidation was 71.1 +/- 11.3 min at week 0 and 81.3 +/- 13.2 min at week 4 (p < 0.05). In vitro studies of LDL oxidation, evaluated by thiobarbituric acid reactive substances (TBARS) and by agarose electrophoretic mobility, indicated that nilvadipine inhibited the oxidative modification of LDL while amlodipine, used as control, did not. Nilvadipine, a lipophilic Ca-antagonist, significantly prolonged the lag time of conjugated diene formation of LDL by 12.6% but amlodipine, a hydrophilic Ca-antagonist, had no major effect on LDL oxidation. These results suggest that Ca-antagonists are effective for the prevention of atherosclerosis but the effect is dependent upon the lipophilicity of the drugs.