Mechanisms of the paradoxical effect of L-Arginine on glomerulosclerosis in 5/6 nephrectomized rats

有争议的whether L-Arginine (L-ARG) ameliorate or aggravate renal functionhistopathological changes in several models of renal diseaseas - arg is the substrate for nitric oxide(NO) synthase as well as the precursor of proline andpolyamines which cause renal fibrosis.这些ambiguous results might be attributed to the differencein the dose and period of L-ARG administeredand animal模型使用在每一个监测. Therefore，we tested the dose-dependent effect of L-ARG on mean blood pressure （MBP）24小时提供蛋白质（UP），NO metabolites (NO - D3-(/) 2d3 +NO - D3-(/) 3d3) and cyclic GMP (cGMP)，plasma dimethylarginine （ADMA）glomerular sclerosis index (SI) and % interstitial fibrosis area (%INT) in 5/6 nephrectomized SDrats. 5/6 nephrectomized SD rats were divided into 4 groups. 1) L-ARG 0.2g/kg/day (0.2gARG) 2) L-ARG1g/kg/day (1gARG) 3) L-ARG 2g/kg/day (2gARG) 4) No administration of L-ARG (ARG(-)). Compared withARG(-) MBP, UP and ADMA were significantly decreased and NO D3-(/) 2d3 +NO D3-(/) 3d3cGMP were significantly increased in 2gARG and %INT were significantly increased in 2gARG and %INTdecreased in 0.2gARG. Small dose of L-ARG ameliorated glomeruiosclerosis and interstitial fibrosiswhile larger dose did not. SI,%INT and ADMA were inversely correlated withNO D3-(/)2 NO D3-(/)3 NO D3-(/)3 NO D3-(/)3 . These data suggested that renal NO synthesis might attenuateglomerulosclerosis and interstitial fibrosis and the rise in ADMA and L-ARG might cause the decreasein no。

It has been still controversial whether L-Arginine (L-ARG) ameliorate or aggravate renal function and histopathological changes in several models of renal disease, as L-ARG is the substrate for nitric oxide(NO) synthase as well as the precursor of proline and polyamines which cause renal fibrosis. These ambiguous results might be attributed to the difference in the dose and period of L-ARG administered, and animal model used in each observation. Therefore, we tested the dose-dependent effect of L-ARG on mean blood pressure (MBP), 24 hour urinary excretion of protein (UP), NO metabolites (NOィイD3-(/)2ィエD3+NOィイD3-(/)3ィエD3) and cyclic GMP (cGMP), plasma asymmetrical dimethylarginine (ADMA), glomerular sclerosis index (SI) and % interstitial fibrosis area (%INT) in 5/6 nephrectomized SD rats. 5/6 nephrectomized SD rats were divided into 4 groups. 1) L-ARG 0.2g/kg/day (0.2gARG) 2) L-ARG 1g/kg/day (1gARG) 3) L-ARG 2g/kg/day (2gARG) 4) No administration of L-ARG (ARG(-)). Compared with ARG(-) MBP, UP and ADMA were significantly decreased and NOィイD3-(/)2ィエD3+NOィイD3-(/)3ィエD3, cGMP were significantly increased in 0.2gARG. SI and %INT were significantly increased in 2gARG and decreased in 0.2gARG. Small dose of L-ARG ameliorated glomeruiosclerosis and interstitial fibrosis while larger dose did not. SI,%INT and ADMA were inversely correlated with NOィイD3-(/)2ィエD3+NOィイD3-(/)3ィエD3. These data suggested that renal NO synthesis might attenuate glomerulosclerosis and interstitial fibrosis and the rise in ADMA and L-ARG might cause the decrease in NO.