Skip to main content
  • Poster presentation
  • Published:

Effects of neuronal nitric oxide synthase in ovine lung injury


Excessive production of nitric oxide is a major factor contributing to acute lung injury and systemic inflammation after burn and smoke inhalation injury. We hypothesized that the use of 7-nitroindazole (7-NI), a selective nNOS inhibitor, blocks molecular mechanisms in this pathogenesis.


Eleven ewes were surgically instrumented and randomly allocated to either an injured untreated control group (40% total body surface area flame burn and 48 breaths of cotton smoke, n = 6), or an injury group treated with 7-NI (1 mg/kg/hour, n = 5).


This insult was associated with systemic inflammation and oxidative stress, as evidenced by a 2.5-fold increase in plasma nitrite/nitrate (NOx) levels, as well as sixfold, twofold, threefold and twofold increases in IL-8, myeloperoxidase (MPO), malondialdehyde (MDA) and poly-ADP-ribose-polymerase (PARP) lung tissue concentrations, respectively. These molecular changes were linked to severe pulmonary derangements. Compared with untreated controls, 7-NI significantly reduced NOx plasma levels (8.4 ± 1 vs 26 ± 10 μmol/l) and decreased IL-8, MPO (3.9 ± 0.2 vs 5.8 ± 0.7 U/g tissue), MDA (2.7 ± 0.3 vs 6.6 ± 1.1 nmol/mg protein) and PARP lung tissue content (3.4 ± 0.7 vs 6.7 ± 0.7), thereby decreasing pulmonary obstruction (12.4 ± 2.2 vs 28.7 ± 5.2 obstruction score) and increasing the PaO2/FiO2 ratio (456 ± 40 vs 313 ± 56, each P < 0.05).


These data suggest that nNOS-derived NO plays a pivotal role in the pathophysiology of this double-hit injury and that selective nNOS inhibition may represent a useful approach to attenuate the degree of pulmonary damage.

Author information

Authors and Affiliations


Rights and permissions

Reprints and permissions

About this article

Cite this article

Saunders, F., Westphal, M., Enkhbaatar, P. et al. Effects of neuronal nitric oxide synthase in ovine lung injury. Crit Care 11 (Suppl 2), P16 (2007).

Download citation

  • Published:

  • DOI: