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 subcutaneously injected aminoguanidine hydrochloride (Ag) (5 mg/100 g/day), during a follow-up period of 6 months. Aminoguanidine effectively prevented albuminuria and albumin extravasation in the mesenteric interstitial tissue (control, 0.43 +/- 0.11 microg EB/100 g of dry tissue, Ag, 0.60 +/- 0.44; untreated diabetic animals, 1.22 +/- 0.73; control and Ag group vs untreated diabetic rats, P < 0.001). Albumin D/P ratio of the aminoguanidine-exposed rats (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 group of animals (0.046 +/- 0.003). Administration of aminoguanidine preserved both submesothelial and subendothelial electronegative charges. For capillary basement membrane (BM), control at zero time, 32 +/- 4 AS/microm BM; control at 6 months, 33.4; aminoguanidine-treated rats, 35 +/- 2. For submesothelial BM, control at zero time, 33 +/- 3; control at 6 months, 32 +/- 3; aminoguanidine-treated rats, 35 +/- 3. Splitting and thickening of both basement membranes were not prevented by the therapeutic intervention. We conclude that the shielding effect of aminoguanidine upon the permselectivity capabilities of the endothelial and mesothelial monolayers appears to be connected, basically to the preservation of anionic fixed charges.
Department of Nephrology & Hypertension, Ha'Emek Medical Center, Afula, Israel.
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Shostak
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Wajsbrot
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Gotloib
D000419:Albuminuria / Q000517:prevention & control; D000818:Animals; D000838:Anions; D001485:Basement Membrane / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D002199:Capillary Permeability / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D004848:Epithelium / Q000187:drug effects / Q000503:physiopathology / Q000648:ultrastructure; D005070:Evans Blue; D006146:Guanidines / Q000494:pharmacology*; D008297:Male; D008854:Microscopy, Electron; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000187:drug effects / Q000503:physiopathology / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000378:metabolism
D000838:Anions; D006146:Guanidines; D012709:Serum Albumin; D005070:Evans Blue; C004479:pimagedine