Human Urinary Bladder Strip Relaxation by the β-Adrenoceptor Agonist Isoprenaline: Methodological Considerations and Effects of Gender and Age.

Abstract

The present study was primarily designed to explore various methodological aspects related to organ bath experiments evaluating human detrusor relaxation by the β-adrenoceptor agonist isoprenaline. Data are based upon a series of 30 consecutive patients, and this cohort was also used to explore possible effects of gender and age. KCl-induced contraction was related to strip length but not weight or cross-sectional area, indicating that the former is most suitable for data normalization. Storage of detrusor strips in cold buffer for up to 2 days did not affect contractile responses to KCl or efficacy of isoprenaline to cause relaxation but significantly affected the isoprenaline potency. No such alterations were observed with up to 1 day of cold storage. The type (KCl vs. passive tension) or strength of contractile stimulus had only minor effects on isoprenaline responses although these differences reached statistical significance in some cases. Similarly, gender and age had only minor if any effects on KCl-induced contraction or isoprenaline-induced relaxation, but the current data are too limited for robust conclusions. In summary we have evaluated experimental conditions for the testing of human detrusor strip contraction and relaxation which should be useful for future larger studies.

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www.frontiersin.org February 2011 | Volume 2 | Article 11 | 1
Original research article
published: 25 February 2011
doi: 10.3389/fphar.2011.00011
Human urinary bladder strip relaxation by the β-adrenoceptor
agonist isoprenaline: methodological considerations and
effects of gender and age
Tim Schneider1†, Charlotte Fetscher1 and Martin C. Michel2*
1 Departments of Urology and Medicine, University of Duisburg-Essen, Essen, Germany
2 Academic Medical Center, Department of Pharmacology and Pharmacotherapy, University of Amsterdam, Amsterdam, Netherlands
The present study was primarily designed to explore various methodological aspects related
to organ bath experiments evaluating human detrusor relaxation by the β-adrenoceptor agonist
isoprenaline. Data are based upon a series of 30 consecutive patients, and this cohort was also
used to explore possible effects of gender and age. KCl-induced contraction was related to
strip length but not weight or cross-sectional area, indicating that the former is most suitable
for data normalization. Storage of detrusor strips in cold buffer for up to 2 days did not affect
contractile responses to KCl or efficacy of isoprenaline to cause relaxation but significantly
affected the isoprenaline potency. No such alterations were observed with up to 1 day of cold
storage. The type (KCl vs. passive tension) or strength of contractile stimulus had only minor
effects on isoprenaline responses although these differences reached statistical significance in
some cases. Similarly, gender and age had only minor if any effects on KCl-induced contraction
or isoprenaline-induced relaxation, but the current data are too limited for robust conclusions.
In summary we have evaluated experimental conditions for the testing of human detrusor strip
contraction and relaxation which should be useful for future larger studies.
Keywords: β3-adrenoceptor, bladder, human, relaxation, method, age, gender
Edited by:
Bimal Malhotra, Pfizer, USA
Reviewed by:
Robert James Theobald, A. T. Still
University of Health Sciences-Kirksville
College of Osteopathic Medicine, USA
Margaret A. Vizzard, University of
Vermont College of Medicine, USA
*Correspondence:
Martin C. Michel, Academisch Medisch
Centrum, Afd. Farmacologie en
Farmacotherapie, Meibergdreef 15,
1105 AZ Amsterdam, Netherlands.
e-mail: m.c.michel@amc.nl
†Present address:
Praxisklinik Urologie Rhein-Ruhr,
Mülheim, Germany.
normalization based upon strip weight (Kories et al., 2003; Monica
et al., 2008; Propping et al., 2010), strip length (Schneider et al.,
2005a; Frazier et al., 2007), or cross-sectional area (Braverman et al.,
2002; Su et al., 2004) have been used, often in the absence of data-
based justification of the chosen approach. Interestingly, group
differences within a study can sometimes be statistically significant
when one normalization approach is chosen but not when another
is applied (Schneider et al., 2005b).
Studies with detrusor tissue from experimental animals have
also indicated that relaxant responses to β-adrenoceptor agonists
may be regulated in several pathophysiological settings; moreo-
ver, differences in relaxant responses may also be attributed to
physiological differences such as those related to gender or aging,
although in most cases such differences were only small (Michel
and Barendrecht, 2008).
For all of the above issues, data on isolated human detrusor are
much scarcer or even absent. On the other hand, direct extrapola-
tion of the existing larger body of animal data is not necessarily
straightforward as relaxation of human detrusor is largely if not
exclusively mediated by β3-adrenoceptors, whereas that of many
animal species involves at least partly other subtypes (Michel and
Vrydag, 2006). As the three β-adrenoceptor subtypes differ in their
regulation pattern (Curran and Fishman, 1996; Guerrero et al.,
1996; Moniotte et al., 2001), specifically studies on physiological
or pathophysiological regulation in animals may not necessarily
be predictive for the human situation as they may reflect differ-
ent receptor subtypes. Moreover, many of the functional regula-
tion studies in animals (Michel and Barendrecht, 2008) have been
INTRODUCTION
Stimulation of β-adrenoceptors is an important mechanism to
increase urinary bladder compliance during the storage phase of
the micturition cycle, i.e., the ability to accommodate increasing
volumes of urine without major elevation in intravesicular pres-
sure (Andersson and Arner, 2004). β-Adrenoceptors can poten-
tially exert their compliance-enhancing effects at the level of the
urothelium (Masunaga et al., 2010), the afferent nerves (Aizawa
et al., 2010), and/or detrusor smooth muscle cells (Michel and
Vrydag, 2006). The latter remain the best established contributor
to bladder compliance as most functional studies of urinary blad-
der β-adrenoceptors have been based upon relaxation of isolated
detrusor strips in an organ bath setting.
Studies with detrusor tissue from animal species have been per-
formed with various types of contractile stimuli, most frequently
based on passive tension or contractile responses induced by mus-
carinic receptor agonists or receptor-independently by KCl. These
studies have indicated that the type of contractile stimulus may
affect the ability of β-adrenoceptor agonists to cause relaxation
(Longhurst and Levendusky, 1999; Frazier et al., 2005; Michel and
Sand, 2009). In contrast, the extent of contractile tone prior to
β-adrenoceptor agonist addition may not importantly affect relaxa-
tion responses (Michel and Sand, 2009), but the currently available
animal data are too limited for reliable conclusions. Given this
uncertainty, it is important to document the strength of contractile
stimulus being used for the relaxation experiments. While most
investigators agree that such data should somehow be normal-
ized for strip size, they disagree how this should be done. Thus,

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Schneider et al. Bladder β-adrenergic responses
otherwise indicated. After 30 min (20 min after KCl), when tension
in KCl-pre-contracted strips had reached a plateau, concentration–
response curves for isoprenaline (1 nM–100 μM) were generated. To
avoid desensitization, only a single relaxation curve was generated
in each bladder strip. As our previous data show that the contractile
response to KCl declines by less than 5% over the time course of
a typical relaxation experiment with rat or human detrusor strips
(Frazier et al., 2005, 2011), no corrections for spontaneous tension
run-down were made.
Force of contraction immediately prior to the addition of the
first agonist concentration within a given experiment was defined
as 0% relaxation, and a force of contraction of 0 mN was defined
as 100% relaxation. If more than one bladder strip from a given
patient was used in a given experiment, the mean of all strips (up
to six) was considered as one experiment unless otherwise stated.
ChemICals
Isoprenaline HCl and all other chemicals were from Sigma-Aldrich
(Munich, Germany).
DaTa aNalysIs
Data are presented as means ± SEM of n experiments. Depending
on the type of analysis, an experiment could be an individual detru-
sor strip or the pooled strips (up to six) of a given patient as indi-
cated. The statistical significance of differences in group means was
determined by paired and un-paired (depending on type of analy-
sis) two-tailed t-tests. The statistical significance of associations
between graded parameters was determined by linear regression
analysis. A p < 0.05 was considered as significant. All curve fitting
and statistical analyses were performed with the Prism program
version 5.1 (GraphPad Software, San Diego, CA, USA).
ResUlTs
KCl-INDUCeD CONTRaCTION
We first analyzed how strip size and storage might affect contractile
responses to KCl. Using only the 34 strips from 23 patients which
had been tested on the day of surgical removal, we did not detect
significant correlations between either strip length, weight or cal-
culated cross-sectional area on the one and the magnitude of the
KCl response on the other hand (data not shown). A similar picture
was also obtained among the strips tested on day 2 (21 strips from
17 patients) or 3 (11 strips from 7 patients). However, if data from
all 66 strips (30 patients) from all 3 days were combined, the KCl
response was weakly but significantly associated with strip length
but not weight or cross-sectional area (Figure 1). Therefore, all
further analyses of KCl responses were based on length-adjusted
force of contraction (mN/mm).
We next explored whether storage for up to 2 days affected the
contractile response to KCl. If only the strips from the patients with
data on day 0 and 1 were considered (16 and 15 strips, respectively,
from 11 patients) or only those with data on day 0 and 2 were con-
sidered (10 and 10 strips, respectively, from six patients), all groups
exhibited very similar contractile responses (Figure 2). Hence, cold
storage for up to 2 days did not affect contractile responses to KCl.
While KCl responses were numerically about a third lower in
strips from female as compared to male patients, the difference
did not reach statistical significance with the limited number of
performed with agonists which activate all β-adrenoceptor sub-
types, i.e., lack information which specific subtype was regulated
functionally. Animal studies with supposedly β3-selective agonists
often are also not conclusive, as many of these compounds lack the
expected selectivity for their target receptor (Vrydag and Michel,
2007). Taken together, a relative large body of evidence regarding
the function and regulation of rodent bladder β-adrenoceptors
contrasts a much more limited knowledge on the human situa-
tion, particularly with regard to regulation under physiological or
pathophysiological conditions.
The discrepancy between a desirability of studies with human
tissue and its relative lack in the published literature at least partly
relates to a limited availability of human tissue to most experimen-
tal investigators. The potential ability to use tissue specimen over
several days may help to explore more of these questions for human
detrusor, as the amount of tissue obtained from a given patient
in many cases is not rate limiting. Therefore, the primary aim of
the present study was to explore how multi-day storage of human
detrusor strips affects contractile responses to KCl and relaxant
responses to the β-adrenoceptor agonist isoprenaline. As second-
ary aims we have explored the role of normalization procedures in
analysis of human contraction data, the role of contractile stimulus
and force for relaxation responses, and finally the roles of gender
and age in contraction and relaxation.
maTeRIals aND meThODs
PaTIeNTs
Human detrusor tissue was from 30 consecutive patients (25 males,
5 females; age of 62.7 ± 1.9 years, range 31–78 years) undergoing
cystectomy due to bladder cancer from macroscopically tumor-free
parts of the bladder after having obtained informed patient consent
based upon a protocol approved by the ethical committee of the
University of Duisburg-Essen. The specimens were transported
to the laboratory within 30 min after surgical removal and muscle
strips were prepared (length 15 ± 4 mm, weight 21 ± 1 mg, n = 66
strips). The cross-sectional area of each strip was calculated based
on weight and length assuming a density of 1 mg/mm3 and was
14.8 ± 0.4 mm2. In some cases, strips were used in the organ bath
on the day of surgical removal (day 0), whereas in other cases strips
were stored in ice-cold buffer for up to 2 days (days 1 and 2).
RelaxaTION sTUDIes
The relaxation studies were performed as previously described
(Frazier et al., 2011). Briefly, bladder strips were mounted under a
resting tension of 10 mN in organ baths containing 10 ml Krebs–
Henseleit buffer of the following composition (mM): NaCl 118.5,
KCl 4.7, MgSO4 1.2, Na4EDTA 0.025, CaCl2 2.5, KH2PO4 1.2,
NaHCO3 25, Hepes 10, and glucose 5.5 at 37°C, yielding a total
potassium concentration of 5.9 mM. The organ baths were con-
tinually gassed with 95% O2/5% CO2 to maintain a pH of 7.4. The
bladder strips were equilibrated for approximately 75 min during
which the buffer solution was refreshed every 15 min. Following
the equilibration, the tissues were challenged with 50 mM KCl
for 6 min and washed again with fresh buffer. They were again
equilibrated and readjusted to a baseline tension of 10 mN every
10 min until stabilization had occurred, usually within 45 min.
After 10 min strips were pre-contracted with 50 mM KCl unless

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Schneider et al. Bladder β-adrenergic responses
youngest patient, who had a very small response, appeared to affect
the correlation analysis; if he was excluded from the analysis, the
inverse association between age and KCl response remained very
weak but became statistically significant (r2 = 0.0934; p = 0.0133)
in the pooled group of both genders.
IsOPReNalINe-INDUCeD RelaxaTION
Isoprenaline concentration-dependently relaxed KCl-contracted
human bladder strips (Figure 4). We first explored whether stor-
age for up to 2 days affected the relaxant response to isoprenaline.
If only the strips from the patients with data on day 0 and 1 were
considered (16 and 15 strips, respectively, from 11 patients), the
potency and efficacy of isoprenaline were very similar and the dif-
ference not statistically significant (p = 0.5879 and 0.2391, respec-
tively, in a paired t-test; Figure 5). A different situation was observed
when looking at patients with data on day 0 and 2 (10 and 10 strips,
respectively, from six patients). While storage for 2 days did not
affect isoprenaline efficacy, it reduced its potency by 0.70 log units
(p = 0.8275 and 0.0017, respectively; Figure 5). Hence, storage
for up to 1 day did not affect relaxant responses, whereas 2-day
storage maintained isoprenaline efficacy but reduced its potency.
Accordingly, only strips from days 0 and 1 were included in the
subsequent analyses.
patients (Figure 3). Pooling data from both genders, KCl responses
tended to decrease with age but this also failed to reach statisti-
cal significance (Figure 3). If only male patients were considered,
the association between age and contraction also lacked statistical
significance (r2 = 0.0349; p = 0.1891). However, in both cases the
Figure 1 | role of normalization of contractile responses to 50 mM KCl
based upon strip length (upper panel), weight (middle panel), or
calculated cross-sectional area (lower panel). Each data represents one
strip (in total 66 strips from 30 patients), and data obtained on days 0–2 were
included.
Figure 2 | effect of storage on contractile responses to 50 mM KCl. Strips
were tested on the day of surgical removal (day 0) or 1 or 2 days later (day 1
and 2). Each data point represents one patient (16 and 15 strips, respectively,
from 11 patients for the day 0 vs. 1 comparison; 10 and 10 strips, respectively,
from 6 patients for the day 0 vs. 2 comparison), whereas the bars represent
the group means. Note that the day 0 patients in the upper panel are not
necessarily the same as in the lower panel, as each panel only shows patients
for whom data on both days were available.

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Schneider et al. Bladder β-adrenergic responses
from five patients as measured on day 0 and 1. While the potency
and efficacy of isoprenaline was numerically higher against pas-
sive tension than against KCl (Figure 4), this difference did not
reach statistical significance (p = 0.0832 and 0.3713, respectively;
Figure 6). We then used the heterogeneity in KCl-induced tension
to explore the role of strength of contractile stimulus. Based upon
54 strips from days 0 and 1, the potency of isoprenaline was not
significantly related to strength of contractile stimulus (r2 = 0.0141;
p = 0.3931); in contrast, the efficacy of isoprenaline was weakly
but significantly associated with contractile tone, i.e., a greater
initial tension was correlated with a greater degree of relaxation
(r2 = 0.1651; p = 0.0023; Figure 7).
Finally, we used our patient series to explore possible differ-
ences in isoprenaline potency or efficacy related to gender or age.
The potency and efficacy of isoprenaline to induce bladder strip
relaxation did not differ significantly between genders (p = 0.2573
and 0.2205, respectively) although efficacy was numerically greater
in males (Figure 8). Similarly, there was no significant association
between age on the one and isoprenaline potency or efficacy on
the other hand (r2 = 0.0224 and p = 0.2757 and r2 = 0.0376 and
p = 0.1561, respectively; Figure 9).
DIsCUssION
The present study has primarily been designed for methodological
validation of techniques to study human isolated detrusor strip
relaxation by the β-adrenoceptor agonist isoprenaline, a response
repeatedly characterized as being predominantly if not exclusively
mediated by the β3-subtype (Michel and Vrydag, 2006; Yamaguchi
and Chapple, 2007). Our main interest in this regard was whether
storage of muscle strips for up to 2 days was possible without affect-
ing contraction or relaxation responses. This was based upon a
series of 30 consecutive patients, many of whom were studied on
multiple days following surgical removal of the bladder specimens.
Findings from these patients were also used to explore effects of
gender and age on such relaxation.
As type and strength of contractile stimulus being used prior to
adding the relaxing agonist may affect its potency and/or efficacy
(Longhurst and Levendusky, 1999; Frazier et al., 2005; Michel and
Sand, 2009), we have initially explored optimal conditions of ana-
lyzing KCl-induced contraction. Even when great care is applied
during the preparation, detrusor strips exhibit some variance in
physical dimensions. As this may affect their ability to contract
and relax, it is generally agreed that some type of normalization
for strips size is required. However, it remains unclear whether
strip weight, length or cross-sectional area is most suitable for
such normalization. Our previous work in rats had demonstrated
that force of contraction correlated to some extent with strip
weight, but the association with strip length was much stronger,
indicating that strip length rather than weight should be used
for normalization (Schneider et al., 2005a). Our present stud-
ies in humans demonstrate that strip length is stronger associ-
ated with KCl-induced force of contraction than strip weight or
cross-sectional area and hence we have used the former for all
subsequent normalization.
The primary question of our study had been whether it is pos-
sible to store human detrusor strips in cold buffer without relevant
alterations of contraction or relaxation. Our data demonstrate that
We next explored the role of type and strength of contractile
stimulus for the isoprenaline-induced relaxation. Paired relaxa-
tion data against passive tension (10 mN) and KCl-induced tone
as assessed within one patient were available for 16 pairs of strips
Figure 3 | effect of gender and age on contractile responses to 50 mM
KCl. Each data point represents one patient (25 males, 5 females, 1–6 strips
per patient), whereas the bars in the upper panel represent the group means.
Figure 4 | relaxation of human detrusor strips by isoprenaline under
passive tension (filled squares) or with tone induced by KCl (open
circles). Data are means ± SEM of five patients for which both conditions
were studied in parallel on day 0 or 1 with 3–4 strips per patient. For
quantitative analysis see main text.

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Schneider et al. Bladder β-adrenergic responses
cause relaxation (Michel and Sand, 2009), but that study was
based on group means of five contractile stimuli, i.e., having
limited statistical power. In the present study such relation-
ships were explored within a single type of contractile stimulus
(50 mM KCl). This did not reveal statistically significant associa-
tions with isoprenaline potency, whereas isoprenaline efficacy
was slightly but significantly associated with starting tension.
These data urge caution when comparing relaxation responses
between two groups of patients, e.g., with and without OAB, if
the starting tension is not the same in both.
Finally, we have used our patient series to explore possible
effects of gender and age on contractile and relaxant responses
in human detrusor. Particularly our data with regard to gender
should be interpreted with caution in this regard as our patient
series contained only five women, and hence was poorly powered to
detect gender differences. While isoprenaline efficacy was numeri-
cally smaller in female than male samples, this difference did not
reach statistical significance. The isoprenaline potency as well as
the contractile responses to KCl also was similar in both genders.
Interestingly, the efficacy of isoprenaline had also been numeri-
cally smaller in female as compared to male rats in a previous
study; while this trend had consistently been observed with four
different agonists including isoprenaline, it had reached statistical
KCl-induced contraction is indeed not affected by storage for up to
2 days. Similarly, cold storage for up to 3 days did not affect con-
tractile responses of isolated arteries to strong stimuli (Kawaguchi
et al., 2010). While the potency and efficacy of isoprenaline to cause
relaxation also was maintained after cold storage for up to 1 day,
storage for 2 days reduced the observed potency of isoprenaline.
Hence, for contraction experiments detrusor strip storage for up
to 2 days may be appropriate, whereas for relaxation experiments
we have limited this to 1 day.
As type or strength of contractile stimulus may affect sub-
sequent relaxation responses in rat detrusor strips (Longhurst
and Levendusky, 1999; Frazier et al., 2005; Michel and Sand,
2009), we have explored this for human detrusor. Confirming
our previous observations in rat bladder (Frazier et al., 2005;
Michel and Sand, 2009), isoprenaline was numerically more
potent but less effective as a relaxing stimulus against passive
tension as compared to KCl-induced detrusor tone. While these
differences did not reach statistical significance in any of these
three studies in rats or humans, the consistency of the find-
ings should form a note of caution when comparing findings
obtained under the two conditions. In previous studies in rats
we had not detected a clear association between strength of
contractile stimulus and potency or efficacy of isoprenaline to
Figure 5 | effect of storage on relaxant responses to isoprenaline,
expressed as potency (peC50) and efficacy (Emax) as calculated per strip.
Strips were tested on the day of surgical removal (day 0) or 1 or 2 days later (day
1 and 2). Each data point represents one patient (16 and 15 strips, respectively,
from 11 patients for the day 0 vs. 1 comparison; 10 and 10 strips, respectively,
from six patients for the day 0 vs. 2 comparison), whereas the bars represent
the group means. Note that the day 0 patients in the upper panel are not
necessarily the same as in the lower panel, as each panel only shows patients
for whom data on both days were available. **p < 0.05 in a paired, two-tailed
t-test vs. corresponding data from day 0.

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Schneider et al. Bladder β-adrenergic responses
Figure 6 | effect of type of contractile stimulus (KCl vs. passive tension)
on the potency and efficacy of isoprenaline to relax human detrusor
strips. Bars describe group means whereas each data point represents one
patient (2–4 strips being tested per patient).
Figure 7 | effect of strength of contractile stimulus on the potency and
efficacy of isoprenaline to relax human detrusor strips. Each data
represents one strip (in total 54 strips from 30 patients), and data obtained on
days 0–1 were included.
Figure 8 | effect of gender (25 males, 5 females) on the potency and
efficacy of isoprenaline to relax human detrusor strips. Bars describe
group means whereas each data point represents one patient (1–4 strips
being tested per patient).
Figure 9 | effect of age on the potency and efficacy of isoprenaline to
relax human detrusor strips. Each data point represents one patient (1–4
strips being tested in each of 30 patients).

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Schneider et al. Bladder β-adrenergic responses
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significance for isoprenaline (Frazier et al., 2006). Rat studies
by other investigators have also yielded equivocal results (Kolta
et al., 1984; Nishimoto et al., 1995; Lluel et al., 2000). Thus, also
for the age question the currently available data are insufficient
for a reliable conclusion.
In conclusion, our study indicates that human detrusor strips
can be stored in cold buffer for at least 1 day without major altera-
tions of isoprenaline potency or efficacy. Our data also emphasize
the need for careful consideration of the contractile stimulus being
used in relaxation experiments and for detailed reporting of the
obtained contraction data. Finally, we conclude that the presently
available evidence is too limited to evaluate possible roles of gender
or age in the human bladder relaxation by β-adrenoceptor agonists.
Hopefully, the protocols developed here will enable larger studies
to answer such questions.
aCKNOwleDgmeNTs
This work was supported in part through Coordination Theme
1 (Health) of the European Community’s FP7, Grant agreement
HEALTH-F2-2008-223234. Tim Schneider was a recipient of a
training fellowship from the intramural grant programme of the
University of Essen Medical School (IFORES).
significance only for the partial agonists BRL 37,344 and CGP
12,177 (Frazier et al., 2006). On the other hand, a study in rabbits
did not detect gender differences in isoprenaline-induced detrusor
relaxation, but within that study relaxation responses in the trigone
were significantly greater in female than male samples (Morita
et al., 1998). Thus, there is insufficient evidence for solid conclu-
sions regarding a possible difference in β-adrenoceptor-mediated
detrusor relaxation.
When exploring possible relationships between age and
contraction and relaxation responses in our patient series, we
observed that such relationships were weak and on an intention-
to-analyze basis not statistically significant. However, the find-
ing that elimination of a single young patient was sufficient to
turn this into a “significant” relationship at least for contraction
indicates that the present number of samples is insufficient for a
robust conclusion. A previous and even smaller study by other
investigators had reported a slightly but significantly smaller
potency and efficacy to cause human detrusor relaxation for
both isoprenaline and BRL 37,344 (Li et al., 2003). In our previ-
ous study in rats all four tested agonists were similarly potent
in young and old animals; however, their efficacy was consist-
ently smaller in old rats although this did not reach statistical

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Frontiers in Pharmacology | Cardiovascular and Smooth Muscle Pharmacology February 2011 | Volume 2 | Article 11 | 8
Schneider et al. Bladder β-adrenergic responses
This article was submitted to Frontiers
in Cardiovascular and Smooth Muscle
Pharmacology, a specialty of Frontiers in
Pharmacology.
Copyright © 2011 Schneider, Fetscher and
Michel. This is an open-access article subject
to an exclusive license agreement between
the authors and Frontiers Media SA, which
permits unrestricted use, distribution, and
reproduction in any medium, provided the
original authors and source are credited.
Received: 06 January 2011; paper pending
published: 01 February 2011; accepted:
16 February 2011; published online: 25
February 2011.
Citation: Schneider T, Fetscher C and
Michel MC (2011) Human urinary blad-
der strip relaxation by the β-adrenoceptor
agonist isoprenaline: methodological con-
siderations and effects of gender and age.
Front. Pharmacol. 2:11. doi: 10.3389/
fphar.2011.00011
Naunyn-Schmiedebergs Arch.
Pharmacol. 374, 385–398.
Yamaguchi, O., and Chapple, C. R. (2007).
β3-Adrenoceptor in urinary bladder.
Neurourol. Urodyn. 26, 752–756.
Conflict of Interest Statement: The
authors declare that the research was con-
ducted in the absence of any commercial
or financial relationships that could be
construed as a potential conflict of interest.
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decreases rabbit bladder smooth
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