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EFFECTS OF ALDOSE REDUCTASE INHIBITION WITH EPALRESTAT ON DIABETES‐INDUCED CHANGES IN RAT ISOLATED ATRIA
Author(s) -
Booth Richard J.,
Hodgson Wayne C.
Publication year - 1993
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1993.tb01672.x
Subject(s) - medicine , endocrinology , isoprenaline , chronotropic , diabetes mellitus , aldose reductase inhibitor , inotrope , basal (medicine) , aldose reductase , stimulation , heart rate , blood pressure
SUMMARY 1. Isoprenaline and cardiac responsiveness of isolated atria from 2 and 6 week streptozotocindiabetic 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 investigated. 2. Spontaneously beating atria, bathed in either normal or high glucose (30 mmol/ L) Krebs’ solution, from both 2 and 6 week diabetic 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 treatment with epalrestat. 3. Isoprenaline (0.1 nmol‐0.1 μmol/L) produced concentration‐dependent increases in inotropy and chronotropy in atria from both control and diabetic rats. 4. Atria from 2 week diabetic rats displayed decreased sensitivity to the positive inotropic effects of isoprenaline. This change was normalized by chronic insulin treatment but not by chronic epalrestat treatment. 5. Atria from 6 week diabetic rats displayed increased sensitivity to the positive chronotropic effects of isoprenaline which was normalized by epalrestat. 6. These 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 contributing factor.