title: Effects of tempol on endothelial and vascular dysfunctions and insulin resistance induced by a high-fat high-sucrose diet in the rat.
abstract: We investigated the effects of treatment with tempol (an antioxidant) on vascular and metabolic dysfunction induced by a high-fat high-sucrose (HFHS) diet. Rats were randomized to receive an HFHS or chow diet with or without tempol treatment (1.5 mmol·(kg body mass)(-1)·day(-1)) for 4 weeks. Blood pressure, heart rate, and blood flow were measured in the rats by using intravascular catheters and Doppler flow probes. Insulin sensitivity and vascular responses to insulin were assessed during a euglycemic-hyperinsulinemic clamp. In-vitro studies were performed to evaluate vascular reactivity and endothelial and inducible nitric oxide synthase (eNOS; iNOS) expression in vascular and muscle tissues. Endothelin, nitrotyrosine, and NAD(P)H oxidase expressions were determined in vascular tissues, and glucose transport activity and glucose transporter 4 (GLUT4) expression were examined in muscles. Tempol treatment was found to prevent alterations in insulin sensitivity, glucose transport activity, GLUT4 expression, and vascular reactivity, and to prevent increases in plasma insulin, blood pressure, and heart rate noted in the untreated HFHS-fed rats. These were associated with increased levels of eNOS expression in vascular and muscle tissues, but reductions in nitrotyrosine, endothelin, NAD(P)H oxidase, and iNOS expressions. Therefore, oxidative stress induced by a relatively short-term HFHS diet could contribute to the early development of vascular and metabolic abnormalities in rats.
authors.affiliation: Endocrinology and Nephrology Axis, CHUQ Research Center from the CHUL, Department of Medicine, Laval University, 2705 Laurier boulevard, Québec, QC G1V 4G2, Canada.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Bourgoin
authors.forename: Hélène
authors.initials: H
authors.lastname: Bachelard
authors.forename: Mylène
authors.initials: M
authors.lastname: Badeau
authors.forename: Richard
authors.initials: R
authors.lastname: Larivière
authors.forename: André
authors.initials: A
authors.lastname: Nadeau
authors.forename: Maryse
authors.initials: M
authors.lastname: Pitre
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D015992:Body Mass Index; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D059305:Diet, High-Fat / Q000009:adverse effects*; D019422:Dietary Sucrose / Q000008:administration & dosage* / Q000009:adverse effects; D019332:Endothelin-1 / Q000378:metabolism; D016232:Endothelins / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D013113:Spin Labels; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D003497:Cyclic N-Oxides; D019422:Dietary Sucrose; D019332:Endothelin-1; D016232:Endothelins; D051275:Glucose Transporter Type 4; D007328:Insulin; C495694:Slc2a4 protein, rat; D013113:Spin Labels; C002744:3-nitrotyrosine; D014443:Tyrosine; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; D019255:NADPH Oxidases; D005947:Glucose; C001803:tempol