INCREASED RESISTANCE TO HYPOXIC CONDUCTION BLOCK IN SCIATIC-NERVES OFDIABETIC RATS - EFFECTS OF EXTRACELLULAR GLUCOSE-CONCENTRATION AND OFALDOSE REDUCTASE INHIBITION

This study examined the effect of the aldose reductase inhibitor (ARI) , ponalrestat, on decreased motor nerve conduction velocity (MNCV) and increased resistance to hypoxic conduction block (RHCB) in diabetic r ats. The effects of 5 mmol/L, and 25 mmol/L glucose on RHCB were also determined. Twenty streptozotocin-diabetic rats formed two groups; unt reated and ponalrestat-treated (300 mg/kg diet/day); 10 non-diabetic r ats acted as controls. MNCV was measured in vivo after 4 weeks of diab etes +/- treatment in the sciatic/tibialis system and rats were killed 48-72 h later. The median nerves were removed and assayed for polyol pathway metabolites by gas chromatography. The sciatic nerves were dis sected to form endoneurial preparations for the recording of compound action potentials (CAPs) in vitro and maintained in media with either 5 (standard) or 25 (high) mmol/L glucose and initially gassed with 95% O2/5% CO2. Oxygen content was then reduced to 8% for 40 min to study the effect of this period of hypoxia on CAP amplitude. MNCV (m/s +/- S D) in diabetic rats (43.86 +/- 4.86) was decreased compared to control s (52.24 +/- 6.59) and this decrease was absent in the ARI-treated gro up (52.24 +/- 6.90). The decline in CAP amplitude during a 40-min hypo xic period was greater in controls than in diabetics. Ponalrestat trea tment caused a decline which was mid-way between these two in standard medium and closer to that seen in control preparations in high glucos e medium. These findings give further support to the involvement of th e sorbitol pathway in the development of the acute MNCV deficit in dia betic rats and indicate that it may have a partial role in the develop ment of increased resistance to hypoxic conduction block in peripheral nerves.