EFFECTS OF ALDOSE REDUCTASE INHIBITION WITH EPALRESTAT ON DIABETES-INDUCED CHANGES IN RAT ISOLATED ATRIA

1. Isoprenaline and cardiac responsiveness of isolated atria from 2 an d 6 week streptozotocin-diabetic rats, and their age-matched controls, was examined. The effects of chronic administration of epalrestat (40 mg/ kg orally, by gavage) on diabetes-induced changes were also inves tigated. 2. Spontaneously beating atria, bathed in either normal or hi gh glucose (30 mmol/L) Krebs' solution, from both 2 and 6 week diabeti c rats beat more slowly and with greater force than atria from control rats. These changes in basal parameters were normalized by 2 weeks of insulin (5 U/day s.c.) treatment but not by 2 or 6 weeks of chronic t reatment with epalrestat. 3. Isoprenaline (0.1 nmol-0.1 mumol/L) produ ced concentration-dependent increases in inotropy and chronotropy in a tria from both control and diabetic rats. 4. Atria from 2 week diabeti c rats displayed decreased sensitivity to the positive inotropic effec ts of isoprenaline. This change was normalized by chronic insulin trea tment but not by chronic epalrestat treatment. 5. Atria from 6 week di abetic rats displayed increased sensitivity to the positive chronotrop ic effects of isoprenaline which was normalized by epalrestat. 6. Thes e results suggest that changes observed in atria from 2 week diabetic rats may be due to hyperglycaemia per se whereas in atria from 6 week diabetic rats abnormal activity of the polyol pathway may be a contrib uting factor.