ALDOSE REDUCTASE INHIBITION WITH IMIRESTAT - EFFECTS ON IMPULSE CONDUCTION AND INSULIN-STIMULATION OF NA+/K+-ADENOSINE TRIPHOSPHATASE-ACTIVITY IN SCIATIC-NERVES OF STREPTOZOTOCIN-DIABETIC RATS

This study describes reduced motor nerve conduction velocity and increased resistance to hypoxia-induced conduction failure in sciatic nerves of rats after four weeks of streptozotocin-induced diabetes (both effects were significant at p < 0.05). These changes occurred in the absence of any deficit in the steady-state ouabain-sensitive adenosine triphosphatase (ATPase) activity of sciatic nerve endoneurial homogenates. The additional of 10 nmol/l insulin to endoneurial homogenates from control animals resulted in a 34% increase in ouabain-sensitive ATPase activity and a 19% reduction in ouabain-insensitive ATPase activity (both p < 0.01). This stimulation of ouabain-sensitive ATPase activity by insulin did not occur in homogenates from diabetic rats. Treating diabetic rats daily with the aldose reductase inhibitor, imirestat (1 mg/kg) improved nerve conduction velocity (p < 0.05) but was without effect upon the resistance to hypoxic conduction blockade or the deficit in insulin-stimulated ouabain-sensitive ATPase activity. These data suggest that in streptozotocin-diabetic rats the functional disorders of reduced motor nerve conduction velocity and increased resistance to hypoxic conduction blockade do not share a common aetiology and that impaired nerve conduction is not related to reduced maximal potential ouabain-sensitive ATPase activity.