Biology Reference
In-Depth Information
volume at voiding desire, maximum detrusor pressure, and voided volume (Truss
et al.
2001
). The hypothesis that detrusor smooth muscle relaxation is mainly
mediated by the cAMP pathway was later supported by a study by Oger et al.
(
2007
), who aimed to determine the effect of rolipram, a PDE4 inhibitor, on
carbachol-induced contractions of human detrusor in vitro. They found that roli-
pram (1 nM-30
m
M) exerted a moderate relaxing effect on the tension induced by
carbachol, but inhibited more effectively the phasic contractile activity of the
tissue. The effect of rolipram on the tonic contraction was enhanced in strips that
had not been denuded of the urothelium or when the production of cAMP was
increased by the adenylyl cyclase activator forskolin. The authors concluded that
PDE4 is involved in the control of the phasic myogenic activity of human bladder
and suggested that PDE4 inhibitors might represent an attractive strategy for
treatment of OAB (Oger et al.
2007
).
Recently, the efficacy of the PDE5 inhibitor vardenafil was also assessed in a
single center, randomized, double-blind, placebo-controlled trial in a group of 25
male patients with spinal cord injuries and with micturition disorders who were on
oxybutynin treatment. Following a baseline urodynamic testing, a second test was
performed 1-3 h after administration of 20 mg vardenafil or placebo. Primary
endpoints were changes in maximum detrusor pressure during voiding, maximum
cystometric capacity, and detrusor volume at first (overactivity) sensation.
Although NO does not appear to have direct smooth muscle regulatory functions
in the detrusor muscle, vardenafil administration significantly decreased maximum
detrusor pressure, considerably improved cystometric capacity, and increased vol-
ume at first sensation (Gacci et al.
2007
).
Thus, modulating the activity of PDE isoenzymes might represent a novel
approach that could avoid the limitations of anticholinergic therapy in patients
with lower urinary tract dysfunction. Future studies will delineate as to whether
PDE inhibitors, such as the PDE1 inhibitor vinpocetine or selective PDE5 inhibi-
tors, may have significance in the treatment of detrusor instabilities and urge
incontinence.
8 Urinary Stone Disease (“Ureteral Colic”)
Verymuch in contrast to the urinary bladder, prostrate or urethra, little is known on the
peripheral neurotransmission responsible for the relaxation of ureteral smooth muscle.
Research on ureteral neurotransmitters focused on afferent innervation; studies on the
efferent limb of the autonomic innervation of the ureter were done over two decades
ago when the concept of nonadrenergic/noncholinergic innervation was not yet
established. From 1990 to 1999, reports on the localization of VIP and NOS in nerves
supplying the ureter were published, but no in vitro studies were done to corroborate
the findings (Smet et al.
1994
). Later, it was demonstrated that the tension of isolated
human ureteral tissue was dose-dependently reversed by the NO donor drug
molsidomine (SIN-1); preincubation with the sGC-inhibitor methylene blue
