Role of nitric oxide in renal function in rats with short and prolonged periods of streptozotocin-induced diabetes

Objective: Nitric oxide (NO) has been proposed to play a significant role i n renal function. In addition, NO production has been found to increase in diabetes mellitus. The present study aimed to clarify the mechanism respons ible for NO action in renal function in rats with short (10 days) or prolon ged periods (8 weeks) of diabetic induction. Methods: Male Wistar rats were induced to develop diabetes mellitus by intr aperitoneal injection of streptozotocin (STZ) (65 mg/kg b.w.), whereas the age-matched control rats were given normal saline. After diabetic induction for 10 days or 8 weeks, the experiment was begun. Three consecutive period s of 30 min each, were designed consisting of one control period, the first and the second period of L-arginine or L-NAME or insulin infusion. Mean ar terial pressure (MAP) was determined every 15 min. Arterial blood and urine samples were collected to determine the plasma glucose level (PG), glomeru lar filtration rate (GFR), effective renal plasma flow (ERPF), urine flow r ate (V), urinary protein excretion (Upro), fractional excretion of glucose (FEG) and fractional excretion of sodium (FENa) in each period. Results: No significant differences of MAP were apparent between control ra ts and rats with diabetic induction. L-arginine infusion had no effect wher eas L-NAME markedly increased MAP in normal rats and rats after the short p eriod of diabetes induction. Pressor response to L-NAME in rats exposed to the prolonged period of diabetes induction was lower than that of age-match ed control rats. During L-NAME infusion, the PG level significantly decline d from 394.9 +/- 13.1-338.0 +/- 14.1 mg/dl and from 399.9 +/- 7.9-354.3 +/- 18.8 mg/dl in rats after short and prolonged periods of diabetic induction , respectively. GFR significantly increased whereas ERPF slightly increased in diabetic rats. The elevation of GFR could be reversed by L-NAME or insu lin infusion but it increased again after simultaneous infusion of insulin and glucose. Increases in V, the Upro and FEG without changes of FENa, were apparent in diabetic rats. Either L-arginine or L-NAME infusion could not reverse elevations of V, Upro and FEG. The rise of both V and Upro was reve rsed along with the attenuation of high FEG during insulin infusion, and it rose again close to the diabetic level during simultaneous infusion of ins ulin and glucose. Elevation of GFR, V and Upro appeared along with a rise o f the PG level by approximate to 300-350 mg/ dl in diabetic rats. Conclusions: Both NO and hyperglycaemia are involved in modulating renal hy perfiltration in diabetic rats. The elevations of urine flow rate and urina ry excretion of both protein and glucose would be expected to represent the reduction of renal tubular reabsorption rather than renal hyperfiltration in diabetic rats. NO does not participate in the change of renal tubular fu nction in diabetic rats. There was a parallel change of urine flow rate and urinary excretion of protein in diabetic rats. The rise of the PG level it self would account for the increases of GFR, V, Upro and FEG in diabetic ra ts. Glomerular hyperfiltration, diuresis and proteinuria in diabetic rats a re not exhibited until the PG level rises to approximate to 300-350 mg/dl.