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NEUROLOGY
& FEMALE UROLOGY
doi: 10.1590/S1677-55382011000200029
Overactive
and underactive bladder dysfunction is reflected by alterations in urothelial
ATP and NO release
Munoz A, Smith CP, Boone TB, Somogyi GT
Laboratory of Neurourology, Scott Department of Urology, Baylor College
of Medicine, Houston, TX, USA
Neurochem Int. 2011; 58: 295-300
- ATP and
NO are released from the urothelium in the bladder. Detrusor overactivity
(DO) following spinal cord injury results in higher ATP and lower NO
release from the bladder urothelium. Our aim was to study the relationship
between ATP and NO release in (1) early diabetic bladders, an overactive
bladder model; and (2) “diuretic” bladders, an underactive
bladder model. To induce diabetes mellitus female rats received 65mg/kg
streptozocin (i.v.). To induce chronic diuresis rats were fed with 5%
sucrose. At 28 days, in vivo open cystometry was performed. Bladder
wash was collected to analyze the amount of ATP and NO released into
the bladder lumen. For in vitro analysis of ATP and NO release, a Ussing
chamber was utilized and hypoosmotic Krebs was perfused on the urothelial
side of the chamber. ATP was analyzed with luminometry or HPLC-fluorometry
while NO was measured with a Sievers NO-analyzer. In vivo ATP release
was increased in diabetic bladders and unchanged in diuretic bladders.
In vitro release from the urothelium followed the same pattern. NO release
was unchanged both in vitro and in vivo in overactive bladders whereas
it was enhanced in underactive bladders. We found that the ratio of
ATP/NO, representing sensory transmission in the bladder, was high in
overactive and low in underactive bladder dysfunction. In summary, ATP
release has a positive correlation while NO release has a negative correlation
with the bladder contraction frequency. The urinary ATP/NO ratio may
be a clinically relevant biomarker to characterize the extent of bladder
dysfunction.
- Editorial
Comment
Munoz et al. report on the importance of urinary ATP/NO ratio as a biomarker
of bladder dysfunction. Nitric oxide has gained importance over recent
years as it has been shown to play an important role on the relaxant
activity of different non striated muscle tissues including bladder,
corpus cavernous and vessels wall. The end product of the nitrergic
pathway is the activation of calcium channels, but a step before that,
cyclic GMP is the trigger element.
Understanding the mechanisms involved in bladder contraction and relaxation
at a molecular level opens new horizons for therapeutic targets and
pharmacological treatments. Not only NO donors may be promising tools
to promote bladder relaxation, but also NO-independent guanilate cyclase
stimulators may become part of this armamentarium.
Reference
- Stasch
JP, Becker EM, Alonso-Alija C, Apeler H, Dembowsky K, Feurer A, et al.:
NO-independent regulatory site on soluble guanylate cyclase. Nature.
2001; 410: 212-5.
- Báu
FR, Mónica FZ, Priviero FB, Baldissera L Jr, de Nucci G, Antunes
E: Evaluation of the relaxant effect of the nitric oxide-independent
soluble guanylyl cyclase stimulator BAY 41-2272 in isolated detrusor
smooth muscle. Eur J Pharmacol. 2010; 637: 171-7.
Dr.
Ricardo Miyaoka
State University Campinas
Campinas, SP, Brazil
E-mail: rmiyaoka@uol.com.br
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