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

Abstract

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.