title: Chronic antioxidant supplementation impairs coronary endothelial function and myocardial perfusion in normal pigs.
abstract: Experimental studies have shown the beneficial effects of antioxidant supplementation on endothelial function in the presence of increased endogenous oxidative stress, whereas limited data are available under normal conditions. The present study tested the hypothesis that in normal pigs long-term antioxidants would have deleterious effects on the cardiovascular system. Normal domestic pigs (V, n=6) were studied 12 weeks after dietary supplementation with vitamin E (100 IU/kg per day) and vitamin C (1 g/day) and compared with normal controls (C, n=7). Myocardial perfusion and permeability index were evaluated by electron beam computed tomography after intravenous adenosine and dobutamine. Coronary endothelial function was evaluated in vitro by organ chamber and coronary tissue studied by immunoblotting and staining. Myocardial perfusion response was lower in V than in C after adenosine (10.1+/-4.5 versus 53.4+/-5.2%; P<0.01) and dobutamine (V, 78.4+/-8.1; C, 193.0+/-39.0%; P<0.05). The permeability index increased in V after adenosine (48.8+/-5.1%) and dobutamine (59.9+/-13.6%) and did not change in C. Coronary vasodilation to bradykinin and substance P was lower in V than in C. Moreover, in V, coronary nitrotyrosine and superoxide content was significantly higher than in C. The groups had similar total monomer expression of endothelial nitric oxide synthase, whereas the dimerized form, reflecting coupled enzyme, was lower in V. These findings suggest that long-term experimental antioxidant vitamin supplementation in normal pigs impairs myocardial perfusion and coronary endothelial function via an increased level of oxidative stress in the arterial wall, which may be partly related to the uncoupling of endothelial nitric oxide synthase and/or the direct prooxidant effect of vitamin radicals.
authors.affiliation: Division of Cardiovascular Diseases, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Daniele
authors.initials: D
authors.lastname: Versari
authors.forename: Elena
authors.initials: E
authors.lastname: Daghini
authors.forename: Martin
authors.initials: M
authors.lastname: Rodriguez-Porcel
authors.forename: Katherine
authors.initials: K
authors.lastname: Sattler
authors.forename: Offer
authors.initials: O
authors.lastname: Galili
authors.forename: Kevin
authors.initials: K
authors.lastname: Pilarczyk
authors.forename: Claudio
authors.initials: C
authors.lastname: Napoli
authors.forename: Lilach O
authors.initials: LO
authors.lastname: Lerman
authors.forename: Amir
authors.initials: A
authors.lastname: Lerman
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage* / Q000494:pharmacology; D001205:Ascorbic Acid / Q000008:administration & dosage* / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D004334:Drug Administration Schedule; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D008833:Microcirculation / Q000187:drug effects; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress; D013552:Swine; D014810:Vitamin E / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D014810:Vitamin E; D052250:Nitric Oxide Synthase Type III; D001205:Ascorbic Acid