Prevention of hypertension, hyperglycemia and vascular oxidative stress by aspirin treatment in chronically glucose-fed rats

Objectives To examine whether an in vivo chronic treatment with aspirin could prevent insulin resistance, oxidative stress and blood pressure elevation associated with high glucose feeding in rats. Methods Sprague-Dawley rats (SD) were given a normal chow diet for 3 weeks combined or not with a 10% glucose drinking solution with or without aspirin added to their drinking water, and were compared to control SD rats which received normal chow and tap water to drink for 3 weeks. Oxidative stress was evaluated by measuring superoxide anion (O-2(-)) production in the aorta using the lucigenin-enhanced chemiluminescence method. Antioxidant reserve was assessed by measuring the activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD) in the blood. Fasting blood sugar and insulin levels were measured at the end of the study. Results The systolic blood pressure (SBP), the aortic basal superoxide production, plasma levels of insulin and glucose, as well as the insulin resistance index, were all significantly higher in rats fed glucose for 3 weeks, compared to control rats. The simultaneous treatment with aspirin prevented the increase in SBP, in plasma glucose levels and in aortic O-2(-) production, and attenuated the rise in insulin levels as well as insulin resistance in the glucose-fed rats. Positive correlations between aortic O-2(-) production and SBP, as well as between insulin resistance and SBP or between O-2(-) production and insulin resistance, were found in control, glucose-fed and aspirin-treated, glucose-fed rats. The activities of GPx and SOD in the erythrocytes did not differ in the three groups. An increase in plasma SOD activity was observed in glucose-fed rats. Conclusions Chronic in vivo treatment with aspirin prevented the development of hypertension and reduced insulin resistance significantly in chronically glucose-fed rats. Aspirin seems to produce these effects through its antioxidative properties, since it was found to prevent the increase in aortic O-2(-) production observed in chronically glucose-fed rats. (C) 2002 Lippincott Williams Wilkins.