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

We hypothesized that an impairment of endothelial dysfunction and an increased response to alpha-adrenoceptor agonists may occur in fructose-fed, insulin-resistant mice. The aim of the present study was to assess the relationship between endothelial dysfunction and agonist-induced contractile responses in such mice. The acetylcholine-induced relaxation was significantly attenuated in streptozotocin-diabetic and fructose-fed mice. The contractile response to noradrenaline was significantly weaker than the control in fructose-fed but not in streptozotocin-diabetic mice; treatment with N(G)-nitro-L-arginine effectively restored this response. Incubating aortic rings with noradrenaline increased the NO(x) [nitrite (NO(2)(-)) and nitrate (NO(3)(-))] level and this level was significantly higher in fructose-fed mice than in control mice. Clonidine induced a dose-dependent relaxation in aortic rings pre-contracted with prostaglandin F(2alpha) that was completely abolished by N(G)-nitro-L-arginine; this relaxation was markedly enhanced in fructose-fed mice. In both control and fructose-fed mice, the clonidine-induced relaxation was significantly attenuated and the noradrenaline-induced contraction augmented 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 fructose-fed mice (compared to both controls and streptozotocin-diabetic mice) may be due to an increase in nitric oxide formation mediated by endothelial GTP-binding-coupled alpha(2)-adrenoceptors.