Oral administration of L-arginine and captopril in rats prevents chronic renal failure by nitric oxide production.
The effect of oral supplementation of L-arginine, the substrate of nitric oxide, (1.25 g/liter water) and captopril (15 mg/liter water) was studied in 5/6 nephrectomized rats for a period of three months. N-omega-nitro L-arginine, a nitric oxide synthase inhibitor, was given orally (70 mg/liter water) with or without L-arginine or captopril. The urinary excretion of nitrite (NO2) + nitrate (NO3), the known metabolites of nitric oxide, was taken as an index of nitric oxide production. Chronic renal failure rats were characterized by a low creatinine clearance, high FENa%, proteinuria, hypertension and a low urinary excretion of NO2 + NO3; 0.152 +/- 0.06 (P < 0.001) nmol/micrograms creatinine compared with 0.481 +/- 0.004 (P < 0.001) in normal rats and 0.479 +/- 0.11 (P < 0.001) in untreated sham-operated rats. Both L-arginine and captopril were effective in the normalization of all these parameters. The combination of L-arginine and captopril had no additive effects. The nitric oxide synthase inhibitor significantly diminished the captopril beneficial effect. It is concluded that chronic renal failure in rats is a low nitric oxide production state. The supplementation of L-arginine is shown to overcome this condition. It is suggested that the beneficial effect of captopril on chronic renal failure is through a specific L-arginine--nitric oxide synthase--nitric oxide pathway.
Ashab
I
I
Department of Nephrology, Tel-Aviv Sourasky Medical Center, Israel.
Peer
G
G
Blum
M
M
Wollman
Y
Y
Chernihovsky
T
T
Hassner
A
A
Schwartz
D
D
Cabili
S
S
Silverberg
D
D
Iaina
A
A
D000284:Administration, Oral; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology*; D003404:Creatinine / Q000378:metabolism; D005260:Female; D007676:Kidney Failure, Chronic / Q000517:prevention & control*; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D009566:Nitrates / Q000652:urine; D009569:Nitric Oxide / Q000096:biosynthesis*; D009573:Nitrites / Q000652:urine; D011507:Proteinuria / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley
D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D001120:Arginine; D002216:Captopril; D003404:Creatinine