Endothelial cell derived relaxing factor has been identified to be nitric oxide and the pathway responsible for its synthesis in human cells has been partially elucidated. Further, antagonists of this pathway have been synthesized and shown to block the hypotension caused by tumor necrosis factor, an important mediator of septic shock. In these investigations, the nitric oxide pathway will be examined in shock and in normal volunteers given endotoxin. We will look for evidence of nitric oxide synthase induction in patients with systemic inflammatory response to clarify the role of this pathway in human disease.
