title: Long-term combined beneficial effects of physical training and metabolic treatment on atherosclerosis in hypercholesterolemic mice.
abstract: The pathogenic mechanisms by which physical exercise influences atherosclerotic lesion formation remain poorly understood. Because vigorous physical training increases oxidative stress, this study tested the hypothesis that graduated and moderate physical exercise together with metabolic intervention (l-arginine and antioxidants) may contribute to increased vascular protection. Exercise training in mice was induced by graduated swimming. In hypercholesterolemic male mice on an atherogenic high-cholesterol diet, graduated and moderate exercise lowered plasma cholesterol and decreased atherosclerotic lesions compared with sedentary control mice. Antioxidants (1.0% vitamin E added to the chow and 0.05% vitamin C added to the drinking water) and l-arginine (6% in drinking water) supplementation to exercising hypercholesterolemic mice further and synergistically reduced atherosclerosis compared with untreated exercised mice. Arterial oxidation-specific epitopes and systemic oxidative stress were reduced by metabolic intervention. Graduated chronic exercise elicited an increase in production of nitric oxide through increased endothelial nitric oxide synthase expression and ameliorated scavenger activities. Thus, metabolic intervention with l-arginine and antioxidants together with graduated and moderate exercise training reduce atherosclerotic lesion formation.
authors.affiliation: Department of General Pathology, Medicine, Clinical Pathology, and Human Pathology, University of Naples, 80131 Naples, Italy. claunap@tin.it
authors.forename: Claudio
authors.initials: C
authors.lastname: Napoli
authors.forename: Sharon
authors.initials: S
authors.lastname: Williams-Ignarro
authors.forename: Filomena
authors.initials: F
authors.lastname: De Nigris
authors.forename: Lilach O
authors.initials: LO
authors.lastname: Lerman
authors.forename: Loredana
authors.initials: L
authors.lastname: Rossi
authors.forename: Carmen
authors.initials: C
authors.lastname: Guarino
authors.forename: Gelsomina
authors.initials: G
authors.lastname: Mansueto
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Tuoro
authors.forename: Orlando
authors.initials: O
authors.lastname: Pignalosa
authors.forename: Gaetano
authors.initials: G
authors.lastname: De Rosa
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Sica
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Ignarro
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001120:Arginine / Q000627:therapeutic use; D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D001205:Ascorbic Acid / Q000627:therapeutic use; D004036:Diet, Atherogenic; D006938:Hyperlipoproteinemia Type II / Q000150:complications* / Q000378:metabolism / Q000628:therapy*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D018384:Oxidative Stress; D010805:Physical Conditioning, Animal; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics; D014810:Vitamin E / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D011973:Receptors, LDL; D014810:Vitamin E; D001120:Arginine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496317:Nos2 protein, mouse; C496315:Nos3 protein, mouse; D001205:Ascorbic Acid