Role of neuronal nitric oxide synthase in ovine sepsis model

Perenlei Enkhbaatar, Matthias Lange, Yoshimitsu Nakano, Atsumori Hamahata, Collette Jonkam, Jianpu Wang, Stefan Jaroch, Lillian Traber, David Herndon, Daniel Traber

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Smoke inhalation injury is often complicated with pneumonia, which frequently leads to subsequent development of sepsis. Excessive NO has been shown to mediate many sepsis-related pathological responses. In the present study, we used our well-established ovine smoke inhalation and pneumonia/sepsis model to examine the hypothesis that neuronal NO synthase (NOS) may be primarily responsible for these pathological alterations. We report the beneficial effects of the specific neuronal NOS (nNOS) inhibitor ZK234238. Adult female sheep were surgically prepared for the study. After 5 to 7 days' recovery, sheep were anesthetized and given double injury: insufflation of 48 breaths of cotton smoke (<40°C) into the airway of each animal and subsequent instillation of live Pseudomonas aeruginosa (5 × 10 colony-forming units) into each sheep's lung via tracheostomy tube. All sheep were mechanically ventilated and fluid resuscitated by lactated Ringer's solution. Sheep were randomly allocated into groups: control (injured not treated, n = 6) and treated (injured, but treated with ZK234238, n = 4). Continuous infusion of ZK234238 (100 μg·kg·h) was started 1 h after insult. ZK234238 attenuated the hypotension (at 18 and 24 h) and fall in systemic vascular resistance (at 24 h) seen in control animals. ZK234238 significantly inhibited increased fluid accumulation as well as increased plasma nitrate/nitrite 24 h after injury. Neuronal NOS inhibition significantly reduced lung water content and attenuated inflammatory indices such as lung tissue myeloperoxidase activity, IL-6 mRNA, and reactive nitrogen species. The above results suggest that the nNOS-derived NO may be involved in the pathophysiology of sepsis-related multiorgan dysfunction.

Original languageEnglish (US)
Pages (from-to)253-257
Number of pages5
Issue number3
StatePublished - Sep 2009


  • Hypotension
  • Sepsis
  • Smoke
  • nNOS

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine


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