To examine if nitric oxide (NO) is produced in radicular cysts, NO syn
thase (NOS) production was analyzed. Periapical tissues were removed f
rom patients at the time of endodontic surgery. Frozen tissue sections
were histologically evaluated with hematoxylin-eosin staining. Produc
tion of human-inducible NOS (iNOS) in apical cysts was then immunohist
ochemically examined. Immunoreactive human iNOS was widely distributed
in epithelial cells, endothelial cells, fibroblasts, macrophages, or
polymorphonuclear leukocytes. Remarkably, iNOS-positive cells were sig
nificantly present around blood vessels, and cells residing apart from
the blood vessels showed weak or no iNOS production, suggesting that
only cells around blood vessels could be stimulated for iNOS synthesis
. These data demonstrated the possibility that several, but not all, c
ells could be stimulated to synthesize iNOS in inflamed tissues. In th
e presence of iNOS, NO can be produced spontaneously in periapical les
ions and may play a crucial role in the regulation of chronic infectio
n.