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 less than 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 addition 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 less than 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 less than 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.
Carrington
A L
AL
Department of Pharmacology, Queen Mary and Westfield College, University of London, UK.
Ettlinger
C B
CB
Calcutt
N A
NA
Tomlinson
D R
DR
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000503:physiopathology*; D004553:Electric Conductivity / Q000187:drug effects / Q000502:physiology; D004594:Electrophysiology; D005449:Fluorenes / Q000494:pharmacology*; D005632:Fructose / Q000032:analysis; D005947:Glucose / Q000032:analysis; D006827:Hydantoins / Q000494:pharmacology*; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology*; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012584:Sciatic Nerve / Q000737:chemistry / Q000201:enzymology / Q000503:physiopathology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013012:Sorbitol / Q000032:analysis; D013311:Streptozocin
D001786:Blood Glucose; D005449:Fluorenes; D006827:Hydantoins; D007328:Insulin; C052241:imirestat; D005632:Fructose; D013012:Sorbitol; D010042:Ouabain; D013311:Streptozocin; D000449:Aldehyde Reductase; D000254:Sodium-Potassium-Exchanging ATPase; D005947:Glucose