ABSTRACT
Isolated rat aortas, after incubation in medium conditioned by endotoxin-stimulated peritoneal macrophages, exhibited diminished contraction to norepinephrine (maximal contraction: control medium = 713 +/- 37 (SE) mg tension/mg tissue; medium conditioned by macrophages = 437 +/- 38, P less than .001). Medium containing endotoxin alone or medium conditioned by nonstimulated macrophages had no effect on aortic tissue response to norepinephrine. Stimulation of peritoneal macrophages in vivo by sterile silica particles also induced diminished contractile responses to norepinephrine by subsequently isolated aortas. Incubation of rat aortas with human monocyte-derived interleukin 1 or recombinant human tumor necrosis factor resulted in diminished aortic contraction and sensitivity to norepinephrine, and gel filtration of medium conditioned by endotoxin-stimulated macrophages yielded suppressive activity at a molecular weight equivalent to interleukin 1 and tumor necrosis factor. The data suggest that mononuclear phagocytes may contribute to altered vascular function in sepsis via the release and vascular modulatory effects of interleukin 1 and tumor necrosis factor.
