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.
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Document Type: Abstract
Affiliations: European Journal of Pharmacology 397: 335–341, 2000. Reprinted with permission from Elsevier Science BV.
Publication date: December 1, 2000