Abstract
The BioBreeding diabetic (BB) rat, a model of insulin dependent diabetes mellitus, is resistant to diabetic nephropathy despite prolonged hyperglycemia. We have previously shown that this resistance is associated with increased urinary excretion of nitric oxide (NO) metabolites and maintenance of high glomerular filtration rates. To assess whether chronic NO synthesis inhibition contributes to the progression of nephropathy, we treated BB rats with nitro-L-arginine-methylester (L-NAME). We studied 4 groups: BioBreeding diabetic rats (BB)(n=12), D + 10 mg/kg L-NAME daily in drinking water (BB+NAME)(n=8), BioBreeding diabetes-resistant controls (C)(n=12), and C+ NAME (n=6). After 6 months of treatment, we measured systolic blood pressure(SBP: mmHg), plasma glucose (Pgluc: mg/dl), creatinine clearance(Ccr: ml/min × 100 g bw), urine protein excretion (UprotV: mg/day × 100 g bw), percent albumin in urine protein (%alb), urine NO metabolite excretion (UNOV: mmol/day × 100 g bw × 103): Table Kidneys were removed and renal NO synthase activity was assayed by conversion of [3H]L-arginine to[3H]L-citrulline (fmol[3H]/min × mg protein). NO synthase activity was similar in BB, BB+NAME and C+NAME (64±12, 66±9, 72.9±9, p=ns) but was significantly higher in C (94±23, p<0.05). Basal renal NO synthase activity in BB rats is low and does not change with chronic NO synthesis inhibition. The maintenance of normal renal function and high urinary NO metabolite excretion may be due to increased systemic rather than renal NO production.
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