NITRIC-OXIDE AND SEPTIC SHOCK - FROM BENCH TO BEDSIDE

Refractory hypotension with end-organ hypoperfusion is an ominous feat ure of inflammatory shock. In the past fifteen years, nitric oxide (a diffusible, short-lived product of arginine metabolism) has been found to be an important regulatory molecule in several areas of metabolism , including vascular tone control. Vascular endothelial cells constitu tively produce low levels of nitric oxide that regulate blood pressure by mediating adjacent smooth-muscle relaxation. In an inflammatory sh ock state, cytokines, like interleukin-1 and tumor necrosis factor-alp ha, induce a separate, high-output form of the enzyme that synthesizes nitric oxide in both endothelial and smooth-muscle cells. The ensuing high rates of nitric oxide formation result in extensive smooth-muscl e relaxation, presser refractory vasodilation, and-ultimately-shock. T he concept of the pathogenesis of inflammatory shock explains many lim itations of current therapies and may foster the development of new in terventions to mitigate the effects of nitric oxide overproduction in this syndrome.