Effect of inhibition of neuronal nitric oxide synthase and L-arginine supplementation on renal ischaemia-reperfusion injury and the renal nitric oxide system

Krisztina Rusai, Andrea Fekete, Beáta Szebeni, Ádám Vannay, Géza Bokodi, Veronika Müller, Ondrej Viklicky, Silvie Bloudickova, Jan Rajnoch, Uwe Heemann, György Reusz, András Szabó, Tivadar Tulassay, Attila J. Szabó

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

1. The role of nitric oxide synthases (NOS) and the nitric oxide (NO) substrate l-arginine in renal ischaemia-reperfusion (I/R) has been studied extensively. However, the results reported are often controversial. In the present study, we examined the effects of the neuronal (n) NOS inhibitor 7-nitroindazole (7-NI) and l-arginine administration on renal I/R injury and the renal NO system in rats. 2. Following 7 days pretreatment with 7-NI (50 mg/kg per day), l-arginine (2 g/kg per day) or vehicle (dimethylsulphoxide : sesame oil, 1 : 9), the left renal vascular pedicles were clamped for 50 min in male Sprague-Dawley rats and kidneys were removed 24 h after reperfusion (n = 7/group). 3. Neither 7-NI nor l-arginine had any effect on parameters of renal function, the grade of tissue injury or the number of terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling (TUNEL)-positive tubular cells compared with vehicle-treated rats. 7-Nitroindazole decreased nNOS mRNA expression and inducible (i) NOS protein levels, but had no effect on endothelial NOS expression. l-Arginine supplementation increased mRNA expression of all NOS isoforms, but only increased protein expression of iNOS. 4. The results of the present study demonstrate that selective inhibition of nNOS has no effect on renal injury, indicating that nNOS does not play a central role in the pathophysiology of renal I/R. In addition, although l-arginine has no effect on renal I/R injury in the model used in the present study, its administration increases the mRNA expression of NOS isoforms.

Original languageEnglish
Pages (from-to)1183-1189
Number of pages7
JournalClinical and Experimental Pharmacology and Physiology
Volume35
Issue number10
DOIs
Publication statusPublished - Oct 1 2008

Keywords

  • 7-nitroindazole
  • Ischaemia/reperfusion
  • Kidney
  • L-arginine
  • Nitric oxide

ASJC Scopus subject areas

  • Physiology
  • Pharmacology
  • Physiology (medical)

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