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Urinary Bladder Dysfunction in Transgenic Sickle Cell Disease Mice.

Claudino MA, Leiria LO, da Silva FH, Alexandre EC, Renno A, Mónica FZ, de Nucci G, Fertrin KY, Antunes E, Costa FF, Franco-Penteado CF - PLoS ONE (2015)

Bottom Line: Cystometry and histomorphometry were also performed in the urinary bladder.Additionally, carbachol, α, β-methylene ATP, KCl, extracellular Ca2+ and electrical-field stimulation promoted smaller bladder contractions in SS group.Histological analyses of SS mice bladder revealed severe structural abnormalities, such as reductions in detrusor thickness and bladder volume, and cell infiltration.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, State University of Campinas, Campinas, SP, Brazil; Laboratory of Multidisciplinary Research, São Francisco University Medical School, Bragança Paulista, SP, Brazil.

ABSTRACT

Background: Urological complications associated with sickle cell disease (SCD), include nocturia, enuresis, urinary infections and urinary incontinence. However, scientific evidence to ascertain the underlying cause of the lower urinary tract symptoms in SCD is lacking.

Objective: Thus, the aim of this study was to evaluate urinary function, in vivo and ex vivo, in the Berkeley SCD murine model (SS).

Methods: Urine output was measured in metabolic cage for both wild type and SS mice (25-30 g). Bladder strips and urethra rings were dissected free and mounted in organ baths. In isolated detrusor smooth muscle (DSM), relaxant response to mirabegron and isoproterenol (1nM-10μM) and contractile response to (carbachol (CCh; 1 nM-100μM), KCl (1 mM-300mM), CaCl2 (1μM-100mM), α,β-methylene ATP (1, 3 and 10 μM) and electrical field stimulation (EFS; 1-32 Hz) were measured. Phenylephrine (Phe; 10nM-100μM) was used to evaluate the contraction mechanism in the urethra rings. Cystometry and histomorphometry were also performed in the urinary bladder.

Results: SS mice present a reduced urine output and incapacity to produce typical bladder contractions and bladder emptying (ex vivo), compared to control animals. In DSM, relaxation in response to a selective β3-adrenergic agonist (mirabegron) and to a non-selective β-adrenergic (isoproterenol) agonist were lower in SS mice. Additionally, carbachol, α, β-methylene ATP, KCl, extracellular Ca2+ and electrical-field stimulation promoted smaller bladder contractions in SS group. Urethra contraction induced by phenylephrine was markedly reduced in SS mice. Histological analyses of SS mice bladder revealed severe structural abnormalities, such as reductions in detrusor thickness and bladder volume, and cell infiltration.

Conclusions: Taken together, our data demonstrate, for the first time, that SS mice display features of urinary bladder dysfunction, leading to impairment in urinary continence, which may have an important role in the pathogenesis of the enuresis and infections observed the SCD patients.

No MeSH data available.


Related in: MedlinePlus

Representative cystometric recording from control (A) and Berkeley transgenic sickle cell (SS) mice (B).Arrows in the cystometric trace indicate the micturition peaks.
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pone.0133996.g001: Representative cystometric recording from control (A) and Berkeley transgenic sickle cell (SS) mice (B).Arrows in the cystometric trace indicate the micturition peaks.

Mentions: In the cystometric study, control mice showed regular micturition cycles with rare non-voiding contractions (n = 8; Table 1; Fig 1A). All of the parameters measured were comparable with our previous data for cystometry in control mice (Leiria et al., 2011). However, homozygous SS mice showed an atypical voiding pattern characterized by an incapacity to produce typical bladder contractions and bladder emptying during a 50-min observation. As shown in Fig 1B, the intravesical pressure during the filling phase increased progressively until reaching a pressure that caused urine leakage (n = 7; Table 1).


Urinary Bladder Dysfunction in Transgenic Sickle Cell Disease Mice.

Claudino MA, Leiria LO, da Silva FH, Alexandre EC, Renno A, Mónica FZ, de Nucci G, Fertrin KY, Antunes E, Costa FF, Franco-Penteado CF - PLoS ONE (2015)

Representative cystometric recording from control (A) and Berkeley transgenic sickle cell (SS) mice (B).Arrows in the cystometric trace indicate the micturition peaks.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4524596&req=5

pone.0133996.g001: Representative cystometric recording from control (A) and Berkeley transgenic sickle cell (SS) mice (B).Arrows in the cystometric trace indicate the micturition peaks.
Mentions: In the cystometric study, control mice showed regular micturition cycles with rare non-voiding contractions (n = 8; Table 1; Fig 1A). All of the parameters measured were comparable with our previous data for cystometry in control mice (Leiria et al., 2011). However, homozygous SS mice showed an atypical voiding pattern characterized by an incapacity to produce typical bladder contractions and bladder emptying during a 50-min observation. As shown in Fig 1B, the intravesical pressure during the filling phase increased progressively until reaching a pressure that caused urine leakage (n = 7; Table 1).

Bottom Line: Cystometry and histomorphometry were also performed in the urinary bladder.Additionally, carbachol, α, β-methylene ATP, KCl, extracellular Ca2+ and electrical-field stimulation promoted smaller bladder contractions in SS group.Histological analyses of SS mice bladder revealed severe structural abnormalities, such as reductions in detrusor thickness and bladder volume, and cell infiltration.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, State University of Campinas, Campinas, SP, Brazil; Laboratory of Multidisciplinary Research, São Francisco University Medical School, Bragança Paulista, SP, Brazil.

ABSTRACT

Background: Urological complications associated with sickle cell disease (SCD), include nocturia, enuresis, urinary infections and urinary incontinence. However, scientific evidence to ascertain the underlying cause of the lower urinary tract symptoms in SCD is lacking.

Objective: Thus, the aim of this study was to evaluate urinary function, in vivo and ex vivo, in the Berkeley SCD murine model (SS).

Methods: Urine output was measured in metabolic cage for both wild type and SS mice (25-30 g). Bladder strips and urethra rings were dissected free and mounted in organ baths. In isolated detrusor smooth muscle (DSM), relaxant response to mirabegron and isoproterenol (1nM-10μM) and contractile response to (carbachol (CCh; 1 nM-100μM), KCl (1 mM-300mM), CaCl2 (1μM-100mM), α,β-methylene ATP (1, 3 and 10 μM) and electrical field stimulation (EFS; 1-32 Hz) were measured. Phenylephrine (Phe; 10nM-100μM) was used to evaluate the contraction mechanism in the urethra rings. Cystometry and histomorphometry were also performed in the urinary bladder.

Results: SS mice present a reduced urine output and incapacity to produce typical bladder contractions and bladder emptying (ex vivo), compared to control animals. In DSM, relaxation in response to a selective β3-adrenergic agonist (mirabegron) and to a non-selective β-adrenergic (isoproterenol) agonist were lower in SS mice. Additionally, carbachol, α, β-methylene ATP, KCl, extracellular Ca2+ and electrical-field stimulation promoted smaller bladder contractions in SS group. Urethra contraction induced by phenylephrine was markedly reduced in SS mice. Histological analyses of SS mice bladder revealed severe structural abnormalities, such as reductions in detrusor thickness and bladder volume, and cell infiltration.

Conclusions: Taken together, our data demonstrate, for the first time, that SS mice display features of urinary bladder dysfunction, leading to impairment in urinary continence, which may have an important role in the pathogenesis of the enuresis and infections observed the SCD patients.

No MeSH data available.


Related in: MedlinePlus