RENAL AND MICROVASCULAR EFFECTS OF AN ALDOSE REDUCTASE INHIBITOR IN EXPERIMENTAL DIABETES

Aldose reductase inhibitors, and particularly sorbinil, have been repo rted to prevent glomerular basement membrane thickening (GBMT) and alb uminuria development in diabetic rats, but contradictory observations have been published. The aim of this study was to answer the following questions (i) is the corrective effect of sorbinil on GBMT, if confir med, associated with an effect on collagen metabolism alterations? (ii ) Is it associated with an effect on microvascular functional alterati ons? We therefore studied the influence of sorbinil on glucosyl-galact osyl-hydroxylysyl-glucohydrolase activity (GGHG; EC 3.2.1.107 which is involved in the catabolism of collagen disaccharide units), 3- and 4- hydroxyproline content and GBMT by ultrastructural morphometry in the kidney cortex of streptozotocin-diabetic rats after 5 months of diseas e. In parallel, the effects on albumin renal clearance and another fun ctional alteration, the microvascular response to norepinephrine, were evaluated. We confirmed a corrective effect of sorbinil on both renal albumin clearance and GBMT. In the diabetic rats, sorbinil diminished the 3-hydroxyproline (but not the 4-hydroxyproline) content, whether expressed per mg protein or per total kidney cortex relative to body w eight. Sorbinil reduced GGHG activity measured in the dialysed 10,000 g supernatant whether expressed per mg protein or per total kidney cor tex; this activity has been shown to be increased in diabetes. Sorbini l also corrected the microvascular response to norepinephrine which is altered in diabetes.