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

Aims/hypothesis. Although increased polyol pathway activity has been implic ated in the pathogenesis of diabetic microangiopathy, the relation with dia betic macroangiopathy remains unclear. Galactose feeding is known to stimul ate the polyol pathway and to develop abnormalities similar to those in dia betic microangiopathy. Our study was conducted to investigate whether an ac tivation of polyol pathway by long-term treatment with galactose produced m orphological changes in coronary arteries of dogs and the effect of an aldo se 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 mont hs, morphometric analyses of coronary arteries were carried out and the gal actitol contents in aortas were measured. Results. The ratio of areas of the intimal layer to those of the medial lay er, an indicator of intimal thickening, was statistically significantly inc reased in galactosefed dogs compared with control dogs. Galactose-fed dogs had a remarkable accumulation of galactitol in their aortas. These morpholo gical and biochemical deficits were reduced by treatment with epalrestat. Conclusion/interpreation. This report morphologically shows diabetes-like m acrovascular abnormalities in galactosaemic animals, suggesting that polyol pathway hyperactivity is closely related to the development of diabetic ma croangiopathy, which could be prevented by aldose reductase inhibition.