Introduction: Endotoxemia leads to induction of inducible nitric oxide synthase (iNOS) and increased expression of numerous inflammatory mediators, contributing to endotoxin‑induced acute lung injury.

Objectives: We examined the hypothesis that supplementation of nitric oxide (NO) with the novel NO donor, S‑nitroso‑human‑serum‑albumin (S‑NO‑HSA), may reduce iNOS expression, lung inflammation and acute lung injury in a rat model of septic shock.

Material and methods: Rats were divided into 4 groups: sham‑operated (no treatment), LPS (lipopolysaccharide), LPS + HSA, and LPS + S‑NO‑HSA. Endotoxin‑induced (20 mg kg–1, iv) lung injury was characterized by measurement of wet/dry weight ratio (pulmonary edema), myeloperoxidase activity (pulmonary neutrophil infiltration), expression of intercellular adhesion molecule‑1, iNOS, and cyclooxygenase‑2.

Results: LPS‑induced acute lung injury involved pulmonary edema, neutrophil infiltration and a strong inflammatory response, resulting in high mortality within 6 h. S‑NO‑HSA prolonged survival of endotoxemic rats, reduced hypotensive response to LPS, and minimized LPS‑induced lung edema by modulation of systemic inflammatory response.

Conclusions: NO supplementation with S‑NO‑HSA after LPS administration prevents induction of iNOS, protects against endotoxin‑induced acute lung injury, and reduces early mortality in endotoxic rats. The results of the study support a therapeutic role of S‑NO‑HSA in the treatment of endotoxemia.