Nephrology Dialysis Transplantation, Vol 14, Issue 6 1398-1407, Copyright © 1999 by Oxford University Press
M Jerkic, J Varagic, D Jovivic, G Radujkovic-Kuburovic, D Nastic-Miric, G Adanja-Grujic, J Markovic-Lipkovski, J Dimitrijevic, Z Miloradovic and S Vojvodic
Background: The pathophysiology of renal ischaemia,
resulting in tubular cell injury and leading to acute renal failure (ARF),
remains unclear. An ever-increasing number of investigations focus on a
possible role of nitric oxide (NO) in regulating circulation during ARF. In
this context, we investigated the influence of chronic stimulation or
inhibition of NO synthesis, or both, on haemodynamic parameters, histology
and plasma renin activity (PRA) after ischaemia-reperfusion injury of rat
kidneys. Methods: Experiments were performed on adult,
male Wistar rats. Before induction of ARF, a group of animals was treated
with a NO synthesis inhibitor (L-NAME) and another
group was treated with a precursor of NO synthesis
(L-arginine). The animals received those substances
for 4 weeks. Control groups received the same amount of tap water for 4 or
8 weeks and were divided into groups with ARF (4 weeks-ARF group and 8
weeks-ARF group) and a sham-operated group. Another group of rats was
treated first with L-NAME and then with
L-arginine in their drinking water, for 4 weeks for
each of these two substances. All parameters were evaluated 24 h after the
induction of ischaemic ARF or the sham operation.
Results: Our results show that such long-term
stimulation of NO release by L-arginine improved
renal haemodynamics in the ischaemic form of ARF. Renal blood flow (RBF)
increased by 96% in the L-arginine-treated rats with
ARF compared with the group with ARF alone. Inhibition of NO synthesis
worsens renal haemodynamics after ARF. However, this aggravation can be
reversed by L-arginine. the rate of water
reabsorption was reduced in all groups with ARF, but this reduction was
least in the grouptreated with L-arginine. The rate
of Na+ reabsorption was reduced in all groups 24 h
after renal ischaemia, but a significant decrease was observed after the
inhibition of NO synthesis. Histological examination of the kidney
specimens showed that morphological changes were least in the rats treated
with L-arginine, when compared with all other groups
with ARF. Nevertheless, the lesions were most prominent in the
L-NAME+ARF group. In this group, the areas of
corticomedullar necrosis were more widespread in comparison with other
groups, especially the L-arginine group where only
swelling of the proximal tubular cells was observed. Treatment with
L-NAME was not accompanied by any significant
alteration in the plasma concentration of angiotensin I (ANG I), while in
the group treated with L-arginine ANG I had a
tendency to decrease. Conclusions: Acute
post-ischaemic renal failure may be alleviated by administering the NO
substrate (L-arginine). NO acts cytoprotectively on
tubular epithelial cells in ischaemia-reperfusion injury of rat kidney.
Evidence of this comes from both histopathological findings and increased
tubular water and sodium reabsorption. However inhibition of NO synthesis
(provoked by L-NAME) worsens renal haemodynamics and
aggravates morphological changes after ARF. These aggravations can,
however, be reversed by L-arginine. Key
words: acute renal failure; angiotensin I; haemodynamics; nitric
oxide; renal morphology
ORIGINAL ARTICLES
L-arginine reduces tubular cell injury in acute post-ischaemic renal failure
Institute for Medical Research, Faculty of Dentistry, Institute of Nuclear Medicine-Clinical Centre, Institute of Pathology Medical School, Military Medical Academy, and Institute of Biophysics, Medical School, Belgrade, Yugoslavia; Corresponding author at: Dr Subotica 4, PO Box 721, 11001 Belgrade, Yugoslavia
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