[Paradoxical effect of L-arginine on nitric oxide (NO) synthesis and histopathological changes in 5/6 nephrectomized SD rats].
Whether L-Arginine (L-ARG) ameliorates or aggravates renal function and histopathological changes in several models of renal disease remains controversial 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 differences in the dose and period of L-ARG administration and the 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 (NO2(-) + NO3-) and cyclic GMP (cGMP), plasma asymmetrical dimethylarginine (ADMA), glomerular sclerosis index (SI) and % interstitial fibrosis area (%INT) in 5/6 nephrectomized SD rats. These 5/6 nephrectomized SD rats were divided into 4 groups: 1. L-ARG 0.2 g/kg/day (0.2 g ARG), 2. L-ARG 1 g/kg/day (1 g ARG), 3. L-ARG 2 g/kg/day (2 g ARG), 4. No administration of L-ARG(ARG(-)). Compared with ARG(-)MBP, UP and ADMA were significantly decreased and NO2(-) + NO3-, cGMP were significantly increased in the 0.2 g ARG. SI group and %INT were significantly increased in the 2 g ARG group and decreased in the 0.2 g ARG group. A small dose of L-ARG ameliorated glomerulosclerosis and interstitial fibrosis while a larger dose did not. SI, %INT and ADMA were inversely correlated with NO2(-) + NO3-. 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.
Tanaka
T
T
Department of Kidney and Dialysis, Hyogo College of Medicine, Japan.
Nakanishi
T
T
Hasuike
Y
Y
Inoue
T
T
Noguchi
K
K
Takamitsu
Y
Y
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D001806:Blood Urea Nitrogen; D005919:Glomerular Filtration Rate; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009392:Nephrectomy; D009569:Nitric Oxide / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley
D009569:Nitric Oxide; D001120:Arginine