Endothelial dysfunction in diabetes mellitus.
In the present study, we examined the pattern of Evan's blue (EB) extravasation over time and we verified the effect of two inhibitors of aldose reductase (sorbinil and ARI 509) as well as aminoguanidine, which modulate nitric oxide (NO) production, on streptozotocin-induced capillary extravasation abnormalities in the upper bronchi, heart, kidney, duodenum, pancreas, skeletal muscle and skin. Albumin extravasation was measured using the EB technique (20 mg/kg). On the third day, a transient decrease in EB leakage was observed in the lung (-49%), heart (-29%) and skeletal muscle (-64%). These early changes in EB were transient, and values returned to normal there after. Later on, EB extravasation was significantly enhanced in the skin (+358, +680, +580, +525 and +365, respectively, at 2, 4, 5, 6 and 7 weeks of diabetes), the duodenum (+101, +160, +92, +124 and +76%), the upper bronchus (+70, +113, +70, +41 and +25%) and the pancreas (+43, +102, +46, +15 and +78%). In the kidney, the increase of EB extravasation was significant at 2 weeks (26%), and from 5 to 7 weeks (+12, +22, +36%). The chronic treatment of diabetic rats with aminoguanidine normalized capillary permeability in most tissues, suggesting that NO is involved in the development of endothelium dysfunction in this streptozotocin-induced diabetic model. Treatment with aldose reductase inhibitors selectively normalized EB extravasation in the kidney.
Chakir
M
M
Department of Pharmacology, Medical School, University of Sherbrooke, Québec, Canada.
Plante
G E
GE
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology*; D004396:Coloring Agents; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D019332:Endothelin-1 / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005070:Evans Blue; D005260:Female; D006146:Guanidines / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D048289:Imidazolidines; D009569:Nitric Oxide / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin; D013012:Sorbitol / Q000378:metabolism
D004396:Coloring Agents; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D006146:Guanidines; D007093:Imidazoles; D048289:Imidazolidines; D012709:Serum Albumin; D009569:Nitric Oxide; D005070:Evans Blue; D013012:Sorbitol; D000449:Aldehyde Reductase; C026411:sorbinil; C004479:pimagedine