Neutrophil accumulation and damage to the gastric mucosa in resuscitated hemorrhagic shock is independent of inducible nitric oxide synthase

Polymorphonuclear leukocytes (PMN) and inducible nitric oxide synthase (iNO S) appear to play important roles in the liver and in lung injury induced b y hemorrhagic shock. Their precise roles in hemorrhagic shock-induced acute gastric mucosal lesions (AGML), however, are still poorly understood. In t his study, we investigated the effect of neutropenia on hemorrhagic shock-i nduced AGML. We also examined the roles of iNOS in PMN infiltration into th e mucosa and AGML during hemorrhagic shock by using L-N-6-(1-iminoethyl)-ly sine, a potent inhibitor of iNOS, and by reverse transcriptase polymerase c hain reaction. Remarkable gastric mucosal damage occurs after hemorrhagic s hock. PMN depletion caused by Vinblastine pretreatment significantly attenu ates this AGML. Although low-dose L-N-6-(1-iminoethyl)-lysine (50 mu g/kg, iNOS inhibition) has no effect on AGML, high-dose L-N-6-(1-iminoethyl)-lysi ne (250 mu g/kg, iNOS + endothelial NOS inhibition) significantly exacerbat es AGML without increasing PMN infiltration into the mucosa, The mRNA expre ssion of iNOS in the stomach during hemorrhagic shock cannot be detected by reverse transcriptase polymerase chain reaction. We conclude that PMN play a pivotal role in hemorrhagic shock-induced AGML, iNOS does not regulate P MN infiltration into the mucosa, and endothelial NOS provides important pro tection against AGML during hemorrhagic shock.