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- Title
Stress causes bladder overactivity in mice: enhanced voiding and detrusor contractility.
- Authors
West, E. G.; Sellers, D. J.; McDermott, C.; Chess-Williams, R.
- Abstract
Introduction: Bladder dysfunction, such as overactive bladder, incontinence and interstitial cystitis, is common in the general population and even more common with age1. A body of clinical evidence exists linking bladder disorders with stress, anxiety and depression, and witness trauma. Stress appears to greatly influence the development of bladder symptoms or worsens the severity of symptoms2,3. In spite of this, there is little research on the precise changes and underlying mechanisms. This study investigates the hypothesis that stress (environmental) in mice causes bladder dysfunction and an overactive bladder phenotype, via mechanisms including altered detrusor contractility. Materials and methods: Female mice (C57BL/6J, 12--14 weeks old) were randomly allocated in to control (n=5) or stress (n=5) experimental groups. In the stress group mice were placed on a central pedestal surrounded by room temperature water for 1hr/day for 10 days, to induce environmental stress due to water avoidance (WAS). Controls were age-matched and housed normally without exposure to environmental stress. Voiding pattern analysis was performed prior to stress (day 0) and on days 1, 3, 5 and 10 of the stress protocol. Mice were euthanised 24 hours after the final stress exposure. Whole bladders were removed, catheterised and intravesical pressure (contractility) recorded during bladder distension following filling of bladders with saline. In addition, the contraction of bladders following stimulation of nerves, and the neurotransmitters involved, were studied, along with contractions caused by the addition of a number of drugs acting at muscarinic, adrenergic and purinergic receptors. Ethical approval: University of Queensland, Animal Ethics Committee (Molecular Biosciences) BOND/536/17 Results: Environmental stress induced an overactive bladder phenotype in mice, causing a significant increase in the number of voiding events observed at all time points tested (Figure 1). Urinary frequency doubled by 24 hours following the first stress exposure (p<0.01) and increased 7-fold (p<0.001) following 10 days of stress. This increase in voiding frequency was associated with a significant decrease in void size but no change in total voided volume. Spontaneous contractility of bladders and bladder contractions evoked by nerve stimulation were not affected by stress. The muscarinic receptor antagonist atropine reduced nerve-evoked bladder contractions similarly in control and stressed mice. However, in the bladders from stressed mice, the involvement of the neurotransmitters nitric oxide and Adenosine Tri-Phosphate (ATP) in nerve-evoked contractions was significantly decreased (nitric oxide: 9.5 ± 3% versus 28.5 ± 5% in control, p0.05) and increased (ATP: 65.9 ± 2% versus 50.5 ± 2% in controls, p<0.05) respectively. Bladders from stressed mice showed greater contractility in response to the muscarinic agonist carbachol (p<0.05), and to the purinergic agonists ATP (p<0.05) and alpha, beta-methylene ATP (p<0.05) compared to controls.
- Subjects
ANIMAL experimentation; DRUGS; MICE; MUSCLE contraction; NEUROTRANSMITTERS; PARASYMPATHOMIMETIC agents; STATISTICAL sampling; PSYCHOLOGICAL stress; URINATION; OVERACTIVE bladder
- Publication
Australian & New Zealand Continence Journal, 2018, Vol 24, Issue 3, p70
- ISSN
1448-0131
- Publication type
Article