Mechanisms underlying attenuated contractile response of aortic rings to noradrenaline in fructose-fed mice

We hypothesized that an impairment of endothelial dysfunction and an increa sed response to alpha -adrenoceptor agonists may occur in fructose-fed, ins ulin-resistant mice. The aim of the present study was to assess the relatio nship between endothelial dysfunction and agonist-induced contractile respo nses in such mice. The acetylcholine-induced relaxation was significantly a ttenuated in streptozotocin-diabetic and fructose-fed mice. The contractile response to noradrenaline was significantly weaker than the control in fru ctose-fed but not in streptozotocin-diabetic mice; treatment with N-G-nitro -L-arginine effectively restored this response. Incubating aortic rings wit h noradrenaline increased the NOx [nitrite (NO2-) and nitrate (NO3-)] level and this level was significantly higher in fructose-fed mice than in contr ol mice. Clonidine induced a dose-dependent relaxation in aortic rings pre- contracted with prostaglandin F-2 alpha that was completely abolished by N- G-nitro-L-arginine; this relaxation was markedly enhanced in fructose-fed m ice. In both control and fructose-fed mice, the clonidine-induced relaxatio n was significantly attenuated and the noradrenaline-induced contraction au gmented by pertussis toxin. These results suggest that endothelial function is attenuated in both fructose-fed and streptozotocin-diabetic mice. It is suggested that the decreased noradrenaline contractile response in fructos e-fed mice (compared to both controls and streptozotocin-diabetic mice) may be due to an increase in nitric oxide fort-nation mediated by endothelial GTP-binding-coupled alpha (2)-adrenoceptors. (C) 2001 Elsevier Science B.V. All rights reserved.