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 journalArticle

21 Citations (Scopus)

Abstract

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
JournalShock
Volume32
Issue number3
DOIs
StatePublished - Sep 2009

Fingerprint

Nitric Oxide Synthase Type I
Sheep
Sepsis
Nitric Oxide Synthase
Smoke
Lung
Pneumonia
Smoke Inhalation Injury
Reactive Nitrogen Species
Insufflation
Tracheostomy
Wounds and Injuries
Nitrites
Vascular Resistance
Nitrates
Hypotension
Pseudomonas aeruginosa
Inhalation
Peroxidase
Interleukin-6

Keywords

  • Hypotension
  • nNOS
  • Sepsis
  • Smoke

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Emergency Medicine

Cite this

Enkhbaatar, P., Lange, M., Nakano, Y., Hamahata, A., Jonkam, C., Wang, J., ... Traber, D. (2009). Role of neuronal nitric oxide synthase in ovine sepsis model. Shock, 32(3), 253-257. https://doi.org/10.1097/SHK.0b013e318193e2ba

Role of neuronal nitric oxide synthase in ovine sepsis model. / Enkhbaatar, Perenlei; Lange, Matthias; Nakano, Yoshimitsu; Hamahata, Atsumori; Jonkam, Collette; Wang, Jianpu; Jaroch, Stefan; Traber, Lillian; Herndon, David; Traber, Daniel.

In: Shock, Vol. 32, No. 3, 09.2009, p. 253-257.

Research output: Contribution to journalArticle

Enkhbaatar, P, Lange, M, Nakano, Y, Hamahata, A, Jonkam, C, Wang, J, Jaroch, S, Traber, L, Herndon, D & Traber, D 2009, 'Role of neuronal nitric oxide synthase in ovine sepsis model', Shock, vol. 32, no. 3, pp. 253-257. https://doi.org/10.1097/SHK.0b013e318193e2ba
Enkhbaatar P, Lange M, Nakano Y, Hamahata A, Jonkam C, Wang J et al. Role of neuronal nitric oxide synthase in ovine sepsis model. Shock. 2009 Sep;32(3):253-257. https://doi.org/10.1097/SHK.0b013e318193e2ba
Enkhbaatar, Perenlei ; Lange, Matthias ; Nakano, Yoshimitsu ; Hamahata, Atsumori ; Jonkam, Collette ; Wang, Jianpu ; Jaroch, Stefan ; Traber, Lillian ; Herndon, David ; Traber, Daniel. / Role of neuronal nitric oxide synthase in ovine sepsis model. In: Shock. 2009 ; Vol. 32, No. 3. pp. 253-257.
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