Progression of micturition dysfunction associated with the development of heart failure in rats: Model of overactive bladder

Progression of micturition dysfunction associated with the development of heart failure in rats: Model of overactive bladder

Heart failure (HF) has a strong association with the development of lower urinary tract symptoms, especially overactive bladder (OAB); although this condition remains poorly investigated. In this study, we assess the aortocaval fistula (ACF) model as a novel experimental model of micturition dysfunc...

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Bibliographic Details
Published in:Life sciences (1973) Vol. 226; pp. 107 - 116
Main Authors: Mora, A.G., Furquim, S.R., Tartarotti, S.P., Andrade, D.R., Janussi, S.C., Krikorian, K., Rocha, T., Franco-Penteado, C.F., Priolli, D.G., Priviero, F.B.M., Claudino, M.A.
Format: Journal Article
Language:English
Published: Netherlands Elsevier Inc 01-06-2019
Elsevier BV
Subjects:
Acetylcholine receptors (muscarinic)
Aortocaval fistula
ATP
Autonomic nervous system
Bladder
Carbachol
Congestive heart failure
Detrusor muscle
Echocardiography
Extracellular matrix
Fistulae
Frequency dependence
Frequency response
Gelatinase B
Gene expression
Heart
Heart failure
Histomorphometry
Micturition
Muscle contraction
Muscles
Overactive bladder
Receptors
Signs and symptoms
Thickness
Transforming growth factor-b
Urinary bladder
Urinary tract
Urination
Urothelium
Ventricle
Heart failure
Overactive bladder
Aortocaval fistula
Micturition
Detrusor muscle
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Summary:Heart failure (HF) has a strong association with the development of lower urinary tract symptoms, especially overactive bladder (OAB); although this condition remains poorly investigated. In this study, we assess the aortocaval fistula (ACF) model as a novel experimental model of micturition dysfunction, associated with HF, focused on the molecular and functional studies to evaluate the autonomic nervous system and urinary bladder remodeling. Male rats were submitted to ACF for HF induction. Echocardiography, cystometric, histomorphometry and molecular analysis, as well as concentration-response curves to carbachol and ATP and frequency-response curves to electrical field stimulation (EFS) were evaluated in Sham and HF (4- and 12-weeksendpoint) groups. Compared to SHAM, HF groups exhibited progressive increases in the left ventricle (LV) mass and fractional shortening which indicates cardiac dysfunction, although HF was characterized only after 12 weeks by the reduced ejection fraction. For micturition function, HF groups presented increased non-voiding contractions (NVC) and decreased bladder capacity; however, when comparing HF groups, these urinary parameters were significantly impaired over the weeks (12-weeks). The contractile responses induced by CCh, ATP and EFS were greater in detrusor muscle (DSM) from HF rats. mRNA expression for muscarinic receptors (M2 and M3) was higher in DSM only after 12 weeks of ACF, in addition to MMP9 and TGF-beta. Histomorphometric revealed increased urothelium thickness in both HF groups, whereas DSM thickness occurred only after 12 weeks. Thus, the ACF model induced cardiac dyfunction with progressive micturition dysfunction over the weeks, characterized by increased DSM contractile mechanisms as well as extracellular matrix remodeling in the urinary bladder, representing a useful tool to evaluate the OAB associated with HF.
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ISSN:0024-3205
1879-0631
DOI:10.1016/j.lfs.2019.04.017