Resuscitation of hemorrhagic shock attenuates intrapulmonary nitric oxide formation.

Hemorrhagic shock has been shown to upregulate intrapulmonary inducible nitric oxide (NO) synthase (iNOS) expression. Increased intrapulmonary iNOS expression is reflected by increases in concentrations of NO in the airways. The purpose of this study was to examine the effects of resuscitation on this induction of intrapulmonary NO formation caused by hemorrhage. Eighteen rats were randomized to one of three groups. One group of rats was simply sham-instrumented and monitored. Two other groups experienced hemorrhagic shock (mean systemic blood pressure of 40-45 mmHg) for 60 min. In one of the hemorrhagic shock groups, resuscitation was performed by re-infusing the shed blood and supplementing it with normal saline. Compared with sham-instrumented rats, those exposed to hemorrhagic shock without subsequent resuscitation exhibited a 10-fold increase in exhaled NO concentrations. Additionally, concentrations of both intrapulmonary iNOS protein and mRNA increased. Resuscitation attenuated the hemorrhage-induced upregulation of exhaled NO, iNOS protein and iNOS mRNA. This data suggests that resuscitation attenuates the hemorrhagic shock-induced formation of intrapulmonary NO by downregulating iNOS transcription. We believe that exhaled NO concentrations provide a useful, non-invasive method of monitoring the intrapulmonary inflammatory sequelae of hemorrhagic shock.