Adrenergic- and capsaicin-evoked nitric oxide release from urothelium and afferent nerves in urinary bladder

Nitric oxide (NO) has been implicated in the regulation of the lower urinary tract. However, the source(s) of NO production in the urinary bladder (UB) has not been determined. Accordingly, we used a porphyrinic microsensor placed on the surface of UB strips in vitro to directly measure endogenous NO production. The afferent neurotoxin, capsaicin, and the mixed alpha/beta-adrenergic agonist, norepinephrine (NE), both evoked transient (1-3 s) NO release (range 50 nM to 1.4 mu M). Adrenergic-mediated release was not decreased following denervation of the UB but was abolished following selective removal of the mucosa. On the other hand, release evoked by capsaicin (range 50-900 nM) was significantly decreased after UB denervation. These data indicate that NE releases NO from UB epithelium, and capsaicin releases NO from epithelium as well as nervous tissue in the UB. In light of reports that NO may regulate epithelial integrity and function in other tissues, agonist regulation of a constitutive nitric oxide synthase activity in the UB may provide a novel mechanism for modulation of bladder and urothelial function.