Protection of vascular wall function in insulin-resistant rats from copper oxidative stress.
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. Nitric oxide-mediated relaxation of noradrenaline-contracted arteries in response to acetylcholine was impaired after 2 h of incubation with Cu(2+) in both genotypes, with or without the continuing presence of Cu(2+). Relaxation was enhanced on initial exposure to Cu(2+), and post-incubation removal of the Cu(2+) resulted in a greater impairment of relaxation. Arteries from cp/cp rats were less impaired in function by Cu(2+) incubation than were those of +/? controls. Sodium nitroprusside-mediated relaxation was impaired by exposure to Cu(2+), with an accompanying increase in EC(50). 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 Cu(2+) incubation was due to oxidative stress. The impairment appears to involve both smooth muscle and the endothelium. 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.
O'Brien
S F
SF
Department of Surgery, University of Alberta, Edmonton, Alberta T6G 2S2, Canada.
Davidge
S T
ST
Zhang
Y
Y
Russell
J C
JC
D000704:Analysis of Variance; D000818:Animals; D002374:Catalase / Q000494:pharmacology; D003300:Copper / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D066298:In Vitro Techniques; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D020011:Protective Agents / Q000494:pharmacology; D051381:Rats; D013482:Superoxide Dismutase / Q000494:pharmacology
D020011:Protective Agents; D009569:Nitric Oxide; D003300:Copper; D002374:Catalase; D013482:Superoxide Dismutase