Nephrology Dialysis Transplantation, Vol 14, Issue 5 1139-1145, Copyright © 1999 by Oxford University Press
L Tome, L Yu, I de Castro, S Campos and A Seguro
Background. The role of nitric oxide (NO) in acute
renal failure (ARF) is not yet completely understood.
L-Arginine (L-arg) is
protective against different ARF models, while L-arg
addition in isolated proximal tubules enhances hypoxia/reoxygenation (H/R)
injury. The aim of this study was to evaluate the effects of
L-arg on renal ischaemia. Methods.
In in vivo studies, Wistar rats were
subjected to 60 min renal artery clamping, and renal function was evaluated
2 and 15 days after ischaemia. Four groups were studied: (1) control; (2)
acute L-arg (50 mg/kg/bw i.v.); (3)
L-nitro-arginine-methyl esther
(L-NAME; 0.5 mg/kg/bw i.v.); and (4) chronic
L-arg (L-arg 0.25% in
drinking water/7 days). For the in vitro studies,
proximal tubules (PTs), isolated by collagenase digestion and Percoll
gradient, were studied from three groups: (1) untreated; (2)
L-arg-treated (L-arg 0.25% in
drinking water/7 days); and (3) L-NAME-treated rats
(3 mg/kg in drinking water/7 days). PTs were kept oxygenated or subjected
to 15 min hypoxia (H-15) and 35 min reoxygenation (R-35). In some
experiments, additional doses of L-arg and
L-NAME were administered. Cell injury was assessed
by lactate dehydrogenase (LDH) release. NO production was evaluated by
NO2-/NO3- measurement (Griess
reaction) in both urine and isolation medium/ Results.
After 2 days, L-arg infusion protected
against ischaemia compared with control rats (0.4 vs
0.2 ml/min/100 g, P<0.001), while neither
L-NAME nor chronic L-arg
supplementation ameliorated renal function. After 15 days, both acute and
chronic L-arg groups showed a higher glomerular
filtration rate (0.6 and 0.75 ml/min/100 g) compared with control rats (0.3
ml/min/100 g, P<0.05) and
L-NAME-treated rats (0.2 ml/min/100 g,
P<0.05). Despite similar recovery in both
L-arg groups, the mortality rate was 25% in the
chronic L group. Tubular function was also better
preserved in the acute L-arg group. PTs isolated
from L-arg-treated rats were more sensitive to
isolation injury. L-Arg addition enhanced H/R injury
(44.9 vs 51.8%, P<0.05),
whereas L-NAME addition protected (44.9
vs 24%, P<0.001) in
untreated rats. In L-arg-treated rats, addition of
L-arg did not enhance H/R injury (49.6
vs 53.5%, NS) and L-NAME was
still protective (49.6 vs 53.5%, NS) and
L-NAME was still protective (49.6
vs 32.3%, P<0.001). In PTs
from L-NAME-treated rats,
L-arg addition also did not enhance H/R injury (50
vs 54%, NS) whereas L-NAME was
protective (50 vs 27%,
P<0.001).
NO2-/NO3- production
paralleled L-arg and L-NAME
supplementation. Conclusion. It was demonstrated that
acute L-arg infusion was beneficial in in
vivo renal ischaemia while it was harmful in isolated H/R
tubules. In contrast, chronic L-arg supplementation
was deleterious both in in vivo and in
vitro renal ischaemia, suggesting that injurious effects had
overcome the beneficial effects during excess NO exposure.
Keywords: acute renal failure;
L-arginine, ischaemia;
L-NAME; nitric oxide; proximal tubules
ORIGINAL ARTICLES
Beneficial and harmful effects of L-arginine on renal ischaemia
Laboratorio de Pesquisa Basica, Department of Nephrology, University of São Paulo School of Medicine, São Paulo, Brazil; Corresponding author
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