Urinary Bladder Dysfunction in Transgenic Sickle Cell Disease Mice

Author(s):Show less -

Claudino, Mario Angelo ^{[1, 2]} ; Silveira Leiria, Luiz Osorio ^[1] ; da Silva, Fabio Henrique ^[3] ; Alexandre, Eduardo Costa ^[1] ; Renno, Andre ^[1] ; Monica, Fabiola Zakia ^[1] ; de Nucci, Gilberto ^[1] ; Fertrin, Kleber Yotsumoto ^[4] ; Antunes, Edson ^[1] ; Costa, Fernando Ferreira ^[3] ; Franco-Penteado, Carla Fernanda ^[3]

Affiliation

^[1] Univ Estadual Campinas, Dept Pharmacol, Campinas, SP - Brazil

^[2] Univ Sao Francisco, Sch Med, Lab Multidisciplinary Res, BR-12900000 Braganca Paulista, SP - Brazil

^[3] Univ Estadual Campinas, Hematol & Hemotherapy Ctr, Campinas, SP - Brazil

^[4] Univ Estadual Campinas, Fac Med Sci, Dept Clin Pathol, Campinas, SP - Brazil

• Document type: Journal article
• Source: PLoS One; v. 10, n. 8 AUG 4 2015.
• Web of Science Citations: 4

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 (1 nM-10 mu M) and contractile response to (carbachol (CCh; 1 nM-100 mu M), KCl (1 mM-300mM), CaCl2 (1 mu M-100mM), alpha,beta-methylene ATP (1, 3 and 10 mu M) and electrical field stimulation (EFS; 1-32 Hz) were measured. Phenylephrine (Phe; 10nM-100 mu M) 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 beta 3-adrenergic agonist (mirabegron) and to a non-selective beta-adrenergic (isoproterenol) agonist were lower in SS mice. Additionally, carbachol, alpha,beta-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. (AU)

• FAPESP's process: 08/57441-0 - Clinical, cellular and molecular alterations in hemoglobinopathies and other hereditary hemolytic anemias
• Grantee: Fernando Ferreira Costa
• Support Opportunities: Research Projects - Thematic Grants