Discordant effects of the aldose resuctase inhibitor, sorbinil, on vascular structure and function in chronically diabetic and galactosemic rats

Abstract

Effects of sorbinil, an aldose reductase inhibitor, were examined on renal glomerular structure, urinary albumin and IgG excretion, and vascular albumin permeation in eyes and aorta of 8-month diabetic, galactose-fed, and age-matched control rats. Sorbinil was added to the diet of one-half of the rats in each group at the time of induction of diabetes and galactosemia. Weight gain was impaired in diabetic and galactose-fed rats versus controls and was improved slightly in corresponding sorbinil-treated groups. Plasma glucose and glycosylated hemoglobin levels, food consumption, and 24-hr urine volume were increased in diabetic rats and were unaffected by sorbinil treatment. Food consumption and glycosylated hemoglobin levels were increased in galactose-fed rats, although the increases were smaller than in diabetic rats; glycosylated hemoglobin levels were decreased by sorbinil. Diabetes- and galactosemia-induced increases in albumin permeation in eyes and aorta were prevented by sorbinil. Urinary excretion of albumin and IgG was increased by diabetes and decreased by sorbinil, although differences between the two diabetic groups were not statistically significant for albumin. Galactosemia was associated with an increase in urinary albumin and IgG excretion that did not reach statistical significance. Glomerular capillary basement membrane width (GBMW) was increased in diabetic versus agematched control rats but was unaffected by galactose feeding. GBMW was increased in controls fed sorbinil and glomerular capillary basement membrane thickening in diabetic rats was not prevented by sorbinil. The fractional volume of the glomerulus occupied by mesangium (V_vmes) was increased in diabetic and galactose fed rats versus agematched controls, and was unaffected by sorbinil. The explanation for the discordant effects of sorbinil on generalized vascular dysfunction versus glomerular structural changes remains unclear.