ATP-sensitive K+ channel effects on nerve function, Na+, K+ ATPase, and glutathione in diabetic rats

Some vasodilators correct nerve conduction velocity and endoneurial blood flow deficits in diabetic rats. It is not known whether vasa nervorum has ATP-sensitive K+ (K-ATP) channels that mediate vasodilation, or whether K-ATP channels could modulate peripheral nerve function. Therefore, we examined the effects of 2 weeks treatment with the K-ATP channel openers, celikalim and WAY135201 (R-4-[3, 4-dioxo-2-(1, 2, 2-trimethyl-propylamino)-cyclobut-1-1-enylamino]-3-methoxy-benzonitrile), on sciatic nerve blood flow, conduction velocity, Na+-K+ ATPase activity and glutathione content after 6 weeks of untreated streptozotocin-diabetes in rats. Blood flow and motor conduction velocity, 47.6% and 20.3% reduced by diabetes, respectively, were completely restored by both celikalim and WAY135201 treatments. Diabetes diminished sciatic Na+-K+ ATPase activity by 47.6% and this was 80-90% corrected by the K-ATP channel openers. Sciatic nerve glutathione content, 30.3% reduced by diabetes, was unaffected by celikalim or WAY135201. Thus, K-ATP channel openers had marked beneficial effects on nerve perfusion and function in experimental diabetic neuropathy, and may be suitable for further study in clinical trials. (C) 2000 Elsevier Science B.V. All rights reserved.