Acute Exposure to Fructose Impairs Endothelium-Dependent Relaxation via Oxidative Stress in Isolated Rat Aortic Rings

Introduction: Although both glucose and fructose are hexoses, their catabolism is quite different: the catabolism of fructose is initiated by ketohexokinase and is not regulated by negative feedback, which results in oxidative stress. Objective: We hypothesized that fructose impairs endothelium-dependent relaxation via oxidative stress in rat aortic rings. Methods: Sprague-Dawley rats were offered 20% fructose solution or tap water for 2 weeks, after which vascular reactivity was measured in isolated aortic rings. In a separate experiment, vascular reactivity was measured after acute exposure to ∼10 mM fructose in isolated aortic rings from untreated rats. Results: Although high-fructose intake statistically significantly increased blood pressure and body weight, it did not affect contraction and relaxation in aortic rings. The substitution of fructose for glucose in Krebs solution inhibited vascular relaxation in aortic rings, which was abolished by pretreatment with antioxidants. Decreasing the glucose concentration in Krebs solution inhibited vascular relaxation, whereas decreasing the fructose concentration in Krebs solution improved vascular relaxation in the aortic rings. Pretreatment with antioxidants improved the vascular relaxation in Krebs solution with fructose substituted for glucose. Conclusions: These results indicate that fructose impairs endothelium-dependent relaxation via oxidative stress in isolated rat aortic rings.