title: Effects of Ca-antagonists on oxidative susceptibility of low density lipoprotein (LDL).
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.
authors.affiliation: First Department of Internal Medicine, National Defense Medical College, Tokorozawa, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yoshida
authors.forename: M
authors.initials: M
authors.lastname: Ayaori
authors.forename: M
authors.initials: M
authors.lastname: Suzukawa
authors.forename: H
authors.initials: H
authors.lastname: Hosoai
authors.forename: M
authors.initials: M
authors.lastname: Nishiwaki
authors.forename: T
authors.initials: T
authors.lastname: Ishikawa
authors.forename: H
authors.initials: H
authors.lastname: Nakamura
mesh_terms: D000328:Adult; D017311:Amlodipine / Q000737:chemistry / Q000494:pharmacology; D001053:Apolipoproteins / Q000097:blood; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D004587:Electrophoresis, Agar Gel; D005227:Fatty Acids / Q000097:blood; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy; D066298:In Vitro Techniques; D008055:Lipids / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood* / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D010084:Oxidation-Reduction; D017392:Thiobarbituric Acid Reactive Substances
chemical_list: D001053:Apolipoproteins; D002121:Calcium Channel Blockers; D005227:Fatty Acids; D008055:Lipids; D008077:Lipoproteins, LDL; D017392:Thiobarbituric Acid Reactive Substances; C035100:nilvadipine; D017311:Amlodipine; D009543:Nifedipine