Diabetic autonomic neuropathy in BB rats and effect of ARI treatment on heart-rate variability and vagus nerve structure.

The preventive effect of the aldose reductase inhibitor (ARI) ponalrestat on heart-rate variability and the development of autonomic neuropathy in the vagus nerve was investigated in the spontaneously diabetic BB rat. ARI treatment completely prevented the characteristic decrease in heart-rate variability and axonal atrophy of the vagus nerve for 4 mo in hyperglycemic BB rats. After 6 mo of treatment, the preventive effect on heart-rate variability was partial, and the vagus nerve demonstrated an increase in regenerating myelinated and unmyelinated fibers. These data suggest that autonomic neuropathy involving the vagus nerve is metabolically induced by demonstrating that inhibition of the polyol pathway significantly delays the occurrence of functional and structural autonomic neuropathy despite the presence of hyperglycemia.