AMINOGUANIDINE AND THE PREVENTION OF LEUKOCYTE DYSFUNCTION IN DIABETES-MELLITUS - A DIRECT VITAL MICROSCOPIC STUDY

1 Defective leukocyte-endothelial interactions are observed in experim ental diabetes mellitus. The present study investigated the effect of aminoguanidine, an inhibitor of advanced glycation end products format ion, on leukocyte-endothelial interactions in alloxan-induced diabetic rats. 2 In rats anaesthetized with sodium pentobarbitone, the interna l spermatic fascia was exteriorized and the microcirculation was obser ved by a closed-circuit TV coupled to a microscope. The number of leuk ocytes rolling along the venular endothelium and sticking to the vascu lar wall was determined after topical application of zymosan-activated plasma (1 mg ml(-1)), as well as the number of adherent and migrated cells after an irritative stimulus (carrageenan 100 mu g). 3 The diabe tic state decreased the number of rolling, sticking and migrated leuko cytes. Pretreatment of diabetic animals with aminoguanidine (250 mg kg (-1) day(-1), for 18 days) normalized these values. To be effective, a minoguanidine had to be administered chronically, starting treatment b efore induction of the diabetic state. 4 The preventive effect was unr elated to the number of circulating leukocytes, or to the hyperglycaem ia or to the hyperosmolality secondary to hyperglycaemia. 5 A non-dial yzed (>12,000-Mr) material in plasma from diabetic, but not normal ani mals, decreased the number of rolling, sticking and migrated leukocyte s in recipient rats. This effect was completely abolished by chronic t reatment of diabetic plasma donors with aminoguanidine. 6 The results suggest that a protein modified by glycosylation (>12 kDa) is associat ed with leukocyte dysfunction in diabetes mellitus and that the abilit y of aminoguanidine to prevent such dysfunction is related to an inhib itory effect on advanced glycation end products formation.