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Departments of 1 Pharmacology and 2 Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15261; and 3 Department of Biomedical Engineering, Duke University, Durham, North Carolina 27508
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
/
-adrenergic agonist, norepinephrine
(NE), both evoked transient (1-3 s) NO release (range 50 nM to 1.4 µM). 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.
constitutive nitric oxide synthase; lower urinary tract; capsaicin-sensitive bladder afferents; epithelium
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