EFFECT OF AMINOGUANIDINE ON IN-VIVO EXPRESSION OF CYTOKINES AND INDUCIBLE NITRIC-OXIDE SYNTHASE IN THE LUNGS OF ENDOTOXEMIC RATS

Endotoxemia results in the release of multiple mediators such as tumor necrosis factor alpha (TNF-proportional to), interleukin-1 beta (IL-1 beta), and nitric oxide (NO), which is thought to be responsible for the hypotension of septic shock. Although there are many reports on th e presence of these mediators in serum, in vivo expression of TNF-prop ortional to, IL-1 beta and inducible nitric oxide synthase (iNOS) at t he tissue level has not been studied extensively. We investigated in v ivo expression of these cytokines and iNOS in the lungs of rats that w ere injected with saline, endotoxin or endotoxin plus aminoguanidine ( AG), an inhibitor of iNOS. Expression of TNF-proportional to, IL-1 bet a and iNOS was absent in control (saline treated) but was increased in endotoxin treated animals. In animals treated with endotoxin plus AG (400 mg/kg), expression of iNOS was markedly inhibited whereas there w as no effect on expression of TNF-proportional to and IL-1 beta. The i nhibitory effect of AG was probably dose dependent because a lower con centration of AG (50 mg/kg) showed no change in the expression of iNOS .