Troglitazone corrects metabolic changes but not vascular dysfunction in dietary-obese rats

Insulin resistance has been attributed to the defect in vascular function a ssociated with obesity, type 2 diabetes and dyslipidaemia. We have investig ated vascular effects of chronic (3-week) administration of troglitazone on female Wistar rats with moderate dietary obesity. Compared with lean contr ols, untreated obese rats had significantly higher body weights, fat pad ma sses, plasma triglycerides, free fatty acids and leptin levels (for all P < 0.01). These metabolic changes were corrected by troglitazone treatment. I n mesenteric arteries, responses to noradrenaline or KCl were similar in al l groups. However, in noradrenaline-preconstricted arteries, vasorelaxation s to acetylcholine and insulin were significantly (50-60% less than in lean , P < 0.001) attenuated in both untreated and troglitazone-treated obese ra ts. Relaxations to sodium nitroprusside showed similar but lesser impairmen t in both untreated and troglitazone-treated obese animals. Our data show t hat although troglitazone markedly improved obesity-induced metabolic chang es, it failed to correct vascular dysfunction associated with obesity in fe male Wistar rats. (C) 2001 Elsevier Science B.V. All rights reserved.