An aldose redutase inhibitor prevents the intimal thickening in coronary arteries of galactose-fed beagle dogs

Abstract

Aims/hypothesis. Although increased polyol pathway activity has been implicated in the pathogenesis of diabetic microangiopathy, the relation with diabetic macroangiopathy remains unclear. Galactose feeding is known to stimulate the polyol pathway and to develop abnormalites similar to those in diabetic microangiopathy. Our study was conducted to investigate whether an activation of polyol pathway by long-term treatment with galactose produced morphological changes in coronary arteries of dogs and the effect of an aldose reductase inhibitor, epalrestat, was also studied. Methods. Dogs received either normal chow or chow containing 30% galactose with or without epalrestat given orally (20 or 50 mg · kg-1). After 44 months, morphometric analyses of coronary arteries were carried out and the galactitol contents in aortas were measured. Results. The ratio of areas of the intimal layer to those of the medial layer, an indicator of intimal thickening, was statistically significantly increased in galactose-fed dogs compared with control dogs. Galactose-fed dogs had a remarkable accumulation of galactitol in their aortas. These morphological and biochemical deficits were reduced by treatment with epalrestat. Conclusion/interpretation. This report morphologically shows diabetes-like macrovascular abnormalities in galactosaemic animals, suggesting that polvol pathway hyperactivity is closely related to the development of diabetic macroangiopathy, which could be prevented by aldose reductase inhibition.