Preservation of endothelium-dependent vascular relaxation in cholesterol-fed rabbit by treatment with the calcium blocker PN 200110

Abstract

We tested the effects of low doses of a dihydropyridine calcium antagonist, PN 200110, on endothelium-dependent vascular relaxation in rabbits fed a 1% cholesterol diet. The drug was given orally, 1 mg/day, and control rabbits received placebo. Plasma total cholesterol after 10 weeks, was similar in the placebo- and PN 200110-treated groups. The respective values averaged 2140 ± 116 (n = 14; mean ± SEM) and 2012 ± 115 mg/dl (n = 13). In placebo-treated rabbits, sudanophilic aortic lesions covered 52 ± 5% of the intimal surface, and the aortic cholesterol concentration was 72 ± 6 mg/g protein. Corresponding values in aortas from PN 2000100-treated rabbits were significantly lower [52 ± 3 mg/g protein (P < 0.03)]. Maximal endothelium-dependent cholinergic relaxation of aortic strips in untreated (n = 14) and treated cholesterol-fed rabbits (n = 13) differed significantly (P < 0.01) and averaged 31 ± 4% and 61 ± 7% of the value in normocholesterolemic controls (n = 13). We conclude that cholesterol feeding suppresses endothelium-dependent relaxation evoked by acetylcholine, and that PN 200110 reduces the severity of atherosclerosis and impairment of endothelium-dependent relaxation.