Beneficial and harmful effects of L-arginine on renal ischaemia

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

Research output: Contribution to journalArticle

52 Citations (Scopus)

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 - 1999
Externally publishedYes

Fingerprint

NG-Nitroarginine Methyl Ester
Arginine
Ischemia
Kidney
Wounds and Injuries
Drinking Water
Nitric Oxide
Acute Kidney Injury
Collagenases
Renal Artery
Glomerular Filtration Rate
L-Lactate Dehydrogenase
Constriction
Hypoxia
Wistar Rats
Digestion
Urine
Mortality

Keywords

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

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Cite this

Beneficial and harmful effects of L-arginine on renal ischaemia. / Tomé, Laura A.; Yu, Luis; De Castro, Isac; Campos-Bilderback, Silvia; Seguro, Antonio C.

In: Nephrology Dialysis Transplantation, Vol. 14, No. 5, 1999, p. 1139-1145.

Research output: Contribution to journalArticle

Tomé, Laura A. ; Yu, Luis ; De Castro, Isac ; Campos-Bilderback, Silvia ; Seguro, Antonio C. / Beneficial and harmful effects of L-arginine on renal ischaemia. In: Nephrology Dialysis Transplantation. 1999 ; Vol. 14, No. 5. pp. 1139-1145.
@article{3f11f85f200f4405911ff884ca90d26b,
title = "Beneficial and harmful effects of L-arginine on renal ischaemia",
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.",
keywords = "Acute renal failure, Ischaemia, L-arginine, L-NAME, Nitric oxide, Proximal tubules",
author = "Tom{\'e}, {Laura A.} and Luis Yu and {De Castro}, Isac and Silvia Campos-Bilderback and Seguro, {Antonio C.}",
year = "1999",
doi = "10.1093/ndt/14.5.1139",
language = "English (US)",
volume = "14",
pages = "1139--1145",
journal = "Nephrology Dialysis Transplantation",
issn = "0931-0509",
publisher = "Oxford University Press",
number = "5",

}

TY - JOUR

T1 - Beneficial and harmful effects of L-arginine on renal ischaemia

AU - Tomé, Laura A.

AU - Yu, Luis

AU - De Castro, Isac

AU - Campos-Bilderback, Silvia

AU - Seguro, Antonio C.

PY - 1999

Y1 - 1999

N2 - 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.

AB - 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.

KW - Acute renal failure

KW - Ischaemia

KW - L-arginine

KW - L-NAME

KW - Nitric oxide

KW - Proximal tubules

UR - http://www.scopus.com/inward/record.url?scp=0032894055&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032894055&partnerID=8YFLogxK

U2 - 10.1093/ndt/14.5.1139

DO - 10.1093/ndt/14.5.1139

M3 - Article

C2 - 10344352

AN - SCOPUS:0032894055

VL - 14

SP - 1139

EP - 1145

JO - Nephrology Dialysis Transplantation

JF - Nephrology Dialysis Transplantation

SN - 0931-0509

IS - 5

ER -