Aminoguanidine reduces regional albumin clearance but not urinary albumin excretion in streptozotocin-diabetic rats.
Advanced glycation end-product-formation is thought to play a role in the development of diabetic angiopathy. By altering the structure of different extracellular matrix components advanced glycation end-products might affect vascular and glomerular permeability. In this study we investigated the effect of treatment with an inhibitor of advanced glycation end-product-formation, aminoguanidine, on vascular permeability and the development of albuminuria in streptozotocin-induced diabetic rats. Male Wistar Rp rats were randomized into a control group, a diabetic group, and an aminoguanidine-treated diabetic group. After 8 weeks, 24-h urine collections were taken and rats were implanted with an arterial and a venous catheter. mean arterial blood pressure was determined by intra-arterial measurement. Regional albumin clearances were assessed in the eye, ileum, lung, skeletal muscle and skin using an isotope technique. Mean arterial pressure in the diabetic group was significantly lower in the control and aminoguanidine-treated groups (p < 0.02). Regional albumin clearances were significantly increased in all tissues of diabetic rats compared to control rats (p < 0.05). Aminoguanidine treatment of diabetic rats resulted in a significant decrease of regional albumin clearance in all tissues except the lung (p < 0.05, lung p = 0.07). The development of albuminuria in diabetic rats however, was not affected by aminoguanidine.
Huijberts
M S
MS
Department of Internal Medicine, University Hospital Maastricht, The Netherlands.
Wolffenbuttel
B H
BH
Crijns
F R
FR
Nieuwenhuijzen Kruseman
A C
AC
Bemelmans
M H
MH
Struijker Boudier
H A
HA
D000419:Albuminuria; D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology / Q000652:urine; D005123:Eye / Q000187:drug effects / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors; D006146:Guanidines / Q000494:pharmacology*; D006801:Humans; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012709:Serum Albumin / Q000493:pharmacokinetics*; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D014018:Tissue Distribution
D017127:Glycation End Products, Advanced; D006146:Guanidines; D012709:Serum Albumin; C004479:pimagedine