The Effects of Arginine and Selective Inducible Nitric Oxide Synthase Inhibitor on Pathophysiology of Sepsis in a CLP Model

Xiao Qi Xie, Yotaro Shinozawa, Junichi Sasaki, Kiyotsugu Takuma, Satoshi Akaishi, Satoshi Yamanouchi, Tomoyuki Endo, Ryosuke Nomura, Michio Kobayashi, Daisuke Kudo, Nobuko Hojo

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)


Background: Sepsis is an arginine-deficient state and is associated with overproduction of nitric oxide (NO) by inducible nitric oxide synthase (iNOS). It has been indicated that low plasma levels of arginine are related to high mortality rates in sepsis. Arginine, however, is also known to be a precursor of NO. Therefore, administration of arginine in septic patients remains controversial. We examined the effects of co-administration of arginine and aminoguanidine, a selective iNOS inhibitor, on sepsis, using rat models. Method: Sepsis was induced in rats by cecal ligation and puncture (CLP). Effects of separate and combined administration of arginine and aminoguanidine were investigated by comparing plasma levels of arginine, expressions of heme oxygenase (HO)-1 and HO-2 in liver and lung, and nitrite + nitrate (NOx) excretion in urine, as well as neuroendocrine responses in urine in the early phase of sepsis. Seven-day survival rates were also examined. Results: A combination of arginine and aminoguanidine recovered the plasma level of arginine at 6 h post-CLP, decreased expression of HO-1 in liver and lung at 24 h post-CLP, decreased urinary excretion of epinephrine, norepinephrine, dopamine, and 17-hydroxycorticosteroid in the first 24 h post-CLP, and increased 7-d survival. Conclusion: It is demonstrated that administration of arginine together with the selective iNOS inhibitor in the early phase of sepsis restores plasma arginine, reduces oxidative stress by probably maintaining NO derived from constitutive NOS, and attenuates neuroendocrine stress responses. This co-administration may be a beneficial treatment approach against sepsis.

Original languageEnglish
Pages (from-to)298-303
Number of pages6
JournalJournal of Surgical Research
Issue number2
Publication statusPublished - 2008 May 15
Externally publishedYes


  • arginine
  • heme oxygenase
  • neuroendocrine system
  • nitric oxide
  • nitric oxide synthase inhibitor
  • sepsis

ASJC Scopus subject areas

  • Surgery


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