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Effects of tempol on endothelial and vascular dysfunctions and insulin resistance induced by a high-fat high-sucrose diet in the rat

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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.
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Keywords: HFHS diet; cardiometabolic complications; complications cardio-métaboliques; diète RGRS; dysfonction endothéliale; endothelial dysfunction; insulin resistance; metabolic syndrome; oxidative stress; résistance à l’insuline; stress oxydant; syndrome métabolique; tempol

Document Type: Research Article

Affiliations: 1: Endocrinology and Nephrology Axis, CHUQ Research Center from the CHUL, Department of Medicine, Laval University, 2705 Laurier boulevard, Québec, QC G1V 4G2, Canada. 2: Division of Nephrology and Hypertension, CHUQ Research Center from the Hôtel-Dieu de Québec, Department of Medicine, Faculty of Medicine, Laval University, Québec, Canada.

Publication date: January 1, 2013

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