ENDOTHELIAL DYSFUNCTION IN DIABETES-MELLITUS

In the present study, we examined the pattern of Evan's blue (EB) extr avasation over time and we verified the effect of two inhibitors of al dose reductase (sorbinil and ARI 509) as well as aminoguanidine, which modulate nitric oxide (NO) production, on streptozotocin-induced capi llary extravasation abnormalities in the upper bronchi, heart, kidney, duodenum, pancreas, skeletal muscle and skin. Albumin extravasation w as measured using the EB technique (20 mg/kg). On the third day, a tra nsient decrease in EB leakage was observed in the lung (-49%), heart ( -29%) and skeletal muscle (-64%). These early changes in EB were trans ient, and values returned to normal there after. Later on, EB extravas ation was significantly enhanced in the skin (+358, +680, +580, +525 a nd +365, respectively, at 2, 4, 5, 6 and 7 weeks of diabetes), the duo denum (+101, +160, +92, +124 and +76%), the upper bronchus (+70, +113, +70, +41 and +25%) and the pancreas (+43, +102, +46, +15 and +78%). I n the kidney, the increase of EB extravasation was significant at 2 we eks (26%), and from 5 to 7 weeks (+12, +22, +36%). The chronic treatme nt of diabetic rats with aminoguanidine normalized capillary permeabil ity in most tissues, suggesting that NO is involved in the development of endothelium dysfunction in this streptozotocin-induced diabetic mo del. Treatment with aldose reductase inhibitors selectively normalized EB extravasation in the kidney.