Protective effect of aminoguanidine upon capillary and submesothelial anionic sites

This study evaluates albuminuria and peritoneal permeability to albumin in control and diabetic rats, as well as in diabetic animals treated with subc utaneously injected aminoguanidine hydrochloride (Ag) (5 mg/100 g/day), dur ing a follow-up period of 6 months. Aminoguanidine effectively prevented al buminuria and albumin extravasation in the mesenteric interstitial tissue ( control, 0.43 +/- 0.11 mug EB/100 g of dry tissue, Ag, 0.60 +/- 0.44; untre ated diabetic animals, 1.22 +/- 0.73; control and Ag group vs untreated dia betic rats, P < 0.001). Albumin D/P ratio of the aminoguanidine-exposed rat s (0.017 +/- 0.011) was higher than that of controls (0.008 +/- 0.002), but significantly lower (P < 0.001) than values observed in the untreated grou p of animals (0.046 +/- 0.003). Administration of aminoguanidine preserved both submesothelial and subendothelial electronegative charges. For capilla ry basement membrane (BM), control at zero time, 32 +/- 4 AS/mum BM; contro l at 6 months, 33.4; aminoguanidine-treated rats, 35 +/- 2. For submesothel ial BM, control at zero time, 33 +/- 3; control at 6 months, 32 +/- 3; amin oguanidine-treated rats, 35 +/- 3. Splitting and thickening of both basemen t membranes were not prevented by the therapeutic intervention. We conclude that the shielding effect of aminoguanidine upon the permselectivity capab ilities of the endothelial and mesothelial monolayers appears to be connect ed, basically to the preservation of anionic fixed charges. (C) 2001 Academ ic Press.