Effects of Chronic α-Adrenergic Receptor Blockade on Peripheral Nerve Conduction, Hypoxic Resistance, Polyols, Na+-K+-ATPase Activity, and Vascular Supply in STZ-D Rats

Abstract

The effects of alpha-receptor blockade on nerve conduction, hypoxic resistance, ouabain-sensitive Na(+)-K(+)-ATPase, nerve polyols, and capillary density were examined in streptozocin-induced diabetic (STZ-D) rats. Nondiabetic and untreated diabetic control groups were used. Diabetes duration was 2 mo. There were two treated diabetic groups. A "prevention" group received 5 mg/kg prazosin for 2 mo from the induction of diabetes. A "reversal" group was untreated for the 1st mo and was given prazosin for the subsequent month. Conduction was measured in motor nerves supplying tibialis anterior and gastrocnemius muscles and sensory saphenous nerve. Diabetes resulted in 15-29% reductions in conduction velocity (P less than 0.01). In the prevention group, conduction deficits were minimal compared with untreated diabetes (P less than 0.01). In the reversal group, motor conduction was also substantially improved, although sensory conduction was not significantly affected. In vitro measurement of sciatic nerve hypoxic resistance revealed a 49% increase in the time taken for compound action potential amplitude to reach half its initial value with diabetes (P less than 0.01). This was largely prevented by prazosin treatment (P less than 0.01), although treatment had a lesser effect in the reversal group. Treatment had no effect on nerve polyol levels or Na(+)-K(+)-ATPase activity. Functional improvements with prazosin were probably based on increased vasa nervorum perfusion. There was a 20% elevation of endoneurial capillary density (P less than 0.01) in both prevention and reversal groups. We conclude that vascular factors play an important role in the etiology of experimental diabetic neuropathy, and functional changes may be corrected by chronic vasodilator treatment.

Effects of Proinsulin C-Peptide in Experimental Diabetic Neuropathy

“…However, whereas nerve Na ϩ ,K ϩ -ATPase activity is reduced in diabetic rats, there is little correlation between this defect and nerve dysfunction. For example, vasodilator treatment improved NCV without any effects on the Na ϩ ,K ϩ -ATPase deficit (37); protein kinase C inhibition also corrected NCV at doses that had no effect on Na ϩ ,K ϩ -ATPase, whereas higher doses corrected the Na ϩ ,K ϩ -ATPase deficit but had deleterious effects on NCV (38). Furthermore, low-dose acetyl carnitine prevented the Na ϩ ,K ϩ -ATPase defect but had no effect on NCV in diabetic rats (39).…”

Treatment of Chronic Painful Diabetic Neuropathy With Isosorbide Dinitrate Spray

“…Recently, several investigators have revealed vasa nervorum angiogenesis in diabetic rats following experiments using vasodilator therapy (15)(16)(17). The vasodilation induced by the increased generation of NO following ISDN treatment may induce angiogenesis of the vasa nervorum, and this may also explain the gradual increase in the analgesic effect of the spray by the end of the first week, which was sustained until treatment was discontinued.…”

Interactions between essential fatty acid, prostanoid, polyol pathway and nitric oxide mechanisms in the neurovascular deficit of diabetic rats

“…Nerve polyols nevertheless remain in the non-diabetic range, thus, a putative "pseudohypoxia" mechanism, based on changes in neuronal NADH/NAD ratio due to flux through the second half of the polyol pathway [41] is unlikely to cause the NCV reduction. Conversely, blood flow and NCV are restored by EPO and vasodilator treatments [2,4,5,19,39] although polyol pathway and pseudohypoxia mechanisms remain strongly activated. Thus, it must be concluded that pseudohypoxia does not contribute significantly to diabetic NCV changes and that neurovascular mechanisms predominate.…”

“…Taken together, these data suggest that a myo-inositol/Na-K ATPase mechanism is unlikely to contribute to the NCV or blood flow results. Furthermore, NCV deficits are corrected by vasodilator or EPO treatments that do not alter Na-K ATPase activity [32,39] and ARI/myo-inositol effects on Na-K ATPase are only found in rats fed a high sucrose diet [4O].…”