Excessive
nitric oxide (NO) formation plays important roles in the pathogenesis of
shock and
multiple organ failure in
sepsis and
acute lung injury (ALI). Evidence from studies in large animal models of
shock provide further insight into the role of NO and the varying
nitric oxide synthase (NOS)
isoforms. Nonselective NOS inhibition in
sepsis models reversed
sepsis-induced derangements in hemodynamic status, but was associated with side effects such as pulmonary vasoconstriction and decreases in global
oxygen delivery. Results from studies on specific inhibition of inducible NOS (iNOS, NOS-2) and neuronal NOS (nNOS, NOS-1) in
sepsis models remain inconclusive, but suggest that both
isoenzymes are involved in the pathophysiological processes. While the long-term effects of NOS inhibition in models of
burn and inhalation injury remain unknown, specific iNOS inhibition attenuated ALI without worsening injury-related
pulmonary hypertension. Further investigation in large animal models is warranted to clarify the time course of increased expression and/or activity of different NOS
isoenzymes and the effects of specific inhibition of the NOS
isoforms at different time points.