Beneficial and harmful effects of L-arginine on renal ischaemia

Laura A. Tomé, Luis Yu, Isac De Castro, Silvia B. Campos, Antonio C. Seguro

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52 Scopus citations

Abstract

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-arg 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 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.

Original languageEnglish (US)
Pages (from-to)1139-1145
Number of pages7
JournalNephrology Dialysis Transplantation
Volume14
Issue number5
DOIs
StatePublished - May 17 1999

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Keywords

  • Acute renal failure
  • Ischaemia
  • L-NAME
  • L-arginine
  • Nitric oxide
  • Proximal tubules

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

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