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A Model of Chronic Nutrient Infusion in the Rat
Published on: August 14, 2013
Troglitazone corrects metabolic changes but not vascular dysfunction in dietary-obese rats
E K Naderali1, L C Pickavance, J P Wilding
1Diabetes and Endocrinology Research Unit, Department of Medicine, University of Liverpool, UCD, Daulby Street, L69 3GA, Liverpool, UK. naderali@liverpool.ac.uk
Abstract:
Insulin resistance has been attributed to the defect in vascular function associated with obesity, type 2 diabetes and dyslipidaemia. We have investigated vascular effects of chronic (3-week) administration of troglitazone on female Wistar rats with moderate dietary obesity. Compared with lean controls, untreated obese rats had significantly higher body weights, fat pad masses, plasma triglycerides, free fatty acids and leptin levels (for all P < 0.01). These metabolic changes were corrected by troglitazone treatment. In mesenteric arteries, responses to noradrenaline or KCl were similar in all groups. However, in noradrenaline-preconstricted arteries, vasorelaxations to acetylcholine and insulin were significantly (50-60% less than in lean, P < 0.001) attenuated in both untreated and troglitazone-treated obese rats. Relaxations to sodium nitroprusside showed similar but lesser impairment in both untreated and troglitazone-treated obese animals. Our data show that although troglitazone markedly improved obesity-induced metabolic changes, it failed to correct vascular dysfunction associated with obesity in female Wistar rats.
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