Nitric oxide synthase (NOS) immunohistochemistry and nicotinamide aden
ine dinucleotide phosphate diaphorase (NADPH-d) histochemistry were us
ed to investigate the distribution of nitroxergic, i.e., nitric oxide-
synthesizing, neuronal perikarya and processes in the human ureteroves
ical junction (UVJ). Tissue specimens obtained from two cadaver kidney
donors and two patients undergoing radical cystectomy for bladder can
cer were examined. Clusters of NOS-immunoreactive neurons were localiz
ed in extramural ureterovesical ganglia. NOS-containing nerve fibers t
raveled within large extramural nerve trunks and marched among smooth
muscle bundles. Extramural and intramural blood vessels were encircled
by varicose NOS-positive axonal processes. The distribution of NOS im
munoreactivity paralleled the staining pattern for NADPH-d activity. U
rothelium stained strongly for NADPH-d activity but showed no NOS immu
nolabeling. Specimens from all four patients investigated showed simil
ar staining patterns. Our results suggest that nitric oxide, a potent
smooth-muscle-relaxing neurotransmitter in the autonomic nervous syste
m, plays a physiologic role in opening the human UVJ.