Protection of vascular wall function in insulin-resistant rats from copper oxidative stress

1 The effects of oxidative stress on vascular function in the insulin-resistant state were assessed in mesenteric resistance arteries of obese, insulin-resistant (cp/cp) and lean, normal (+/?) JCR : LA-cp rats. 2 Nitric oxide-mediated relaxation of noradrenaline-contracted arteries in response to acetylcholine was impaired after 2 h of incubation with Cu2+ in both genotypes, with or without the continuing presence of Cu2+. Relaxation was enhanced on initial exposure to Cu2+ and post-incubation removal of the Cu2+ resulted in a greater impairment of relaxation. Arteries from cp/cp rats were less impaired in function by Cu2+ incubation than were those of + /? controls. 3 Sodium nitroprusside-mediated relaxation was impaired by exposure to Cu2+, with an accompanying increase in EC50. 4 The impairment in acetylcholine-mediated relaxation in the arteries: from both cp/cp and +/? rats was completely inhibited by co-incubation with copper-zinc superoxide dismutase and catalase, confirming that the impairment associated with Cu2+ incubation was due to oxidative stress. 5 The impairment appears to involve both smooth muscle and the endothelium. 6 The cp/cp rats showed greater resistance to the effects of oxidative stress on arterial function, possibly due to an adaptation to oxidative stress on arterial function associated with the insulin resistant state.