What are the origins and relevance of spontaneous bladder contractions? ICI-RS 2017

Introduction: Storage phase bladder activity is a counter-intuitive observation of spontaneous contractions. They are potentially an intrinsic feature of the smooth muscle, but interstitial cells in the mucosa and the detrusor itself, as well as other muscular elements in the mucosa may substantially influence them. They are identified in several models explaining lower urinary tract dysfunction. Methods: A consensus meeting at the International Consultation on Incontinence Research Society (ICI-RS) 2017 congress considered the origins and relevance of spontaneous bladder contractions by debating which cell type(s) modulate bladder spontaneous activity, whether the methodologies are sufficiently robust, and implications for healthy and abnormal lower urinary tract function. Results: The identified research priorities reflect a wide range of unknown aspects. Cellular contributions to spontaneous contractions in detrusor smooth muscle are still uncertain. Accordingly, insight into the cellular physiology of the bladder wall, particularly smooth muscle cells, interstitial cells, and urothelium, remains important. Upstream influences, such as innervation, endocrine, and paracrine factors, are particularly important. The cellular interactions represent the key understanding to derive the integrative physiology of organ function, notably the nature of signalling between mucosa and detrusor layers. Indeed, it is still not clear to what extent spontaneous contractions generated in isolated preparations mirror their normal and pathological counterparts in the intact bladder. Improved models of how spontaneous contractions influence pressure generation and sensory nerve function are also needed. Conclusions: Deriving approaches to robust evaluation of spontaneous contractions and their influences for experimental and clinical use could yield considerable progress in functional urology

The effect of indomethacin on the muscarinic induced contractions in the isolated normal guinea pig urinary bladder

<p>Abstract</p> <p>Background</p> <p>To investigate the effect of prostaglandin depletion by means of COX-inhibition on cholinergic enhanced spontaneous contractions.</p> <p>Methods</p> <p>The urethra and bladder of 9 male guinea pigs (weight 270–300 g) were removed and placed in an organ bath with Krebs’ solution. A catheter was passed through the urethra through which the intravesical pressure was measured. The muscarinic agonist arecaidine, the non-selective COX inhibitor indomethacin, and PGE₂ were subsequently added to the organ bath. The initial average frequency and amplitude of spontaneous contractions in the first 2 minutes after arecaidine application were labelled F_ini and P_ini, respectively. The steady state frequency (F_steady) and amplitude (P_steady) were defined as the average frequency and amplitude during the 5 minutes before the next wash out.</p> <p>Results</p> <p>Application of 1 μM PGE₂ increased the amplitude of spontaneous contractions without affecting frequency. 10 μM of indomethacin reduced amplitude but not frequency.</p> <p>The addition of indomethacin did not alter F_ini after the first application (p = 0.7665). However, after the second wash, F_ini was decreased (p = 0.0005). F_steady, P_steady and P_ini were not significantly different in any of the conditions. These effects of indomethacin were reversible by PGE₂ addition._.</p> <p>Conclusions</p> <p>Blocking PG synthesis decreased the cholinergically stimulated autonomous contractions in the isolated bladder. This suggests that PG could modify normal cholinergically evoked response. A combination of drugs inhibiting muscarinic receptors and PG function or production can then become an interesting focus of research on a treatment for overactive bladder syndrome.</p