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Abstract This study investigated the potentially protective effect of PPAR-γ stimulants against diabetes and insulin resistance-induced vascular dysfunction and illustrated the mechanism of this protection. Two animals’ models were used; diabetes was induced by a single intraperitonial injection of streptozotocin (STZ 50 mg/kg). Insulin resistance (IR) was induced in rats (100-120g) by adding fructose (10%) to the drinking water and both models were associated with vascular dysfunction after 8 and 12 weeks respectively. In this study, the protective role of PPAR-γ stimulation by chronic oral administration of PPAR-γ agonists, rosiglitazone and pioglitazone (5and 10 mg/kg respectively, daily, last 6weeks) on vascular complication in IR animals. The effect of rosiglitazone on diabetic vascular complication was also investigated. In addition, we evaluated the effect of natural PPAR-γ agonists, chrysin and luteolin administration (25 and 100 mg/kg respectively, daily oral, last 6weeks) against vascular complications in both diabetic and IR animal models. To confirm that the protective effect is mediated by PPAR-γ stimulation activities, the PPAR-γ antagonist BADGE (15 mg/kg, oral) was co-administered with chrysin or luteolin. At the end of study, non-invasive blood pressure (BP) was recorded to determine the systolic, diastolic and pulse. Serum levels of glucose, advanced glycation end products (AGEs), triglycerides, total and LDL cholesterol were determined. Contractile responses of isolated aorta to phenylephrine (PE), KCl, and relaxation response to acetylcholine (ACh) were obtained. ACh-induced NO and KCl-induced Ca2+ influx in aorta were also studied. |