RENAL RESPONSE TO VOLUME EXPANSION IN STREPTOZOTOCIN-INDUCED DIABETICRATS - INFLUENCE OF CALCIUM-CHANNEL BLOCKADE

The renal response to volume expansion (VE) has been shown to be impai red in streptozotocin (STZ)-induced diabetes. This may contribute to t he abnormal maintenance of fluid balance in diabetics. Since calcium c hannel blockade (CaCb) has been shown to improve renal hemodynamic and tubular functions, the present studies were designed to examine the a bility of CaCb to enhance the response of kidneys from diabetic rats t o a volume load. Rats were made diabetic by a single injection of STZ (65 mg i.p.), while the control rats received only a vehicle injection . Nisoldipine, a CaCb agent was given to half of the diabetic rats in a dose of 0.015 mu g/kg per min during the acute experiment. The left kidney was denervated in each rat while the right kidney remained inne rvated. Glomerular filtration rate (GFR) was elevated during VE in all of the rats except in the denervated kidneys of diabetic rats. Nisold ipine improved GFR in most cases. Urine flow increased markedly during VE. This response was enhanced by denervation but depressed in the di abetic rats. Nisoldipine improved the defective volume reflex in prima rily the denervated kidneys. Changes in net urinary excretion of water and sodium during VE were significantly lower in the diabetic rats th an in the control group. In the nisoldipine treated diabetic rats the VE induced changes in water and sodium excretion returned toward norma l in the denervated, but not in the innervated kidneys. The data are c onsistent with a blunted volume reflex in the diabetic rats that may b e improved by CaCb. Impaired spmpatho-inhibition in diabetic rats appe ars to oppose the effects of VE and nisoldipine treatment. CaCb may co ntribute to the volume reflex by enhanced filtration as well as by red uced tubular reabsorption. (C) 1997 EIsevier Science Ireland Ltd.