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-+ ++benzonitri le), 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.