Role of nitric oxide in hemorrhagic shock-induced bacterial translocation

Background. Hemorrhagic shock-induced bacterial translocation is an etiolog ic factor in the pathogenesis of multiple system organ damage. Excessive pr oduction of nitric oxide (NO) during hemorrhagic shock may lead to cellular injury and gut barrier failure that promotes bacterial translocation. We i nvestigated the effect of aminoguanidine (AG) and NG-nitro-L-arginine methy l ester (L-NAME), both inhibitors of NO synthase, on hemorrhagic shock- ind uced bacterial translocation in the rat. Materials and methods. Anesthetized male Sprague-Dawley rats were subjected to a hemorrhagic shock protocol for 30 min followed by intravenous injecti on (1 mL/kg body wt) with normal saline, AG; (100 mg/kg), or L-NAME (10 mg/ kg). Tissues/organs were examined histologically for damage and bacterial t ranslocation. Plasma nitrate/nitrite was measured using a procedure based o n the Griess reaction, and nitric oxide synthase (NOS) expression was deter mined immunohistochemically. Results. The shocked animals treated with saline died within 90 min, and de aths were associated with 100% bacterial translocation, increased tissue/or gan damage, and elevated nitrate/nitrite production. In contrast, both AG a nd L-NAME increased the survival time of shocked rats to >72 h, abrogated b acterial translocation, reduced tissue/organ damage, and prevented excessiv e nitrate/nitrite production and upregulation of expression of endothelial NOS and inducible NOS. Conclusions. Prevention of bacterial translocation by pharmacologic agents such as aminoguanidine and L-NAME could be an important therapeutic approac h to lessen mortality rates following hemorrhagic shock. (C) 2000 Academic Press.