Aminoguanidine reduces regional albumin clearance but not urinary albumin excretion in streptozotocin-diabetic rats

Abstract

Summary 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 endproducts might affect vascular and glomerular permeability. In this study we investigated the effect of treatment with an inhibitor of advanced glycation endproduct-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. [Diabetologia (1994) 37: 10-14]Key words Diabetes mellitus, rat, advanced glycation end-products, aminoguanidine, vascular permeability, albuminuria.The formation of advanced glycation end-products (AGEs) on long-lived macromolecules has been implicated in the aetiology of diabetic angiopathy. Numerous reports have shown that AGE-formation can alter the function of several systems that are involved in cardiovascular homeostasis [1].Extracellular matrix components such as type IV collagen and laminin undergo marked structural changes following glycation [2,3]. The observed alterations might influence the interaction of these components with other basement membrane elements such as Alterations in the density of HS-PG in glomerular basement membrane and the vascular wall are thought to play a role in the development of both glomerular and systemic permeability changes in diabetes [4,5]. Increases in vascular permeability and increase in urinary albumin excretion have been shown to develop simultaneously in both clinical and experimental diabetes [6][7][8][9].Aminoguanidine, a nucleophilic hydrazine compound, prevents the formation of AGEs [10]. This drug has been shown to decrease albuminuria in spontaneously hypertensive diabetic rats [11]. In addition, experiments in a skin-chamber model suggest that it can reduce the increased vascular permeability induced by hyperglycaemia [12]. We hypothesized that a beneficial effect of aminoguanidine would also imply reduction of increased regional albumin clearance in other organs. Therefore, in this study we assessed the effects of aminoguanidine treatm...