A Refocus on the Bladder as the Originator of Storage Lower Urinary Tract Symptoms: A Systematic Review of the Latest Literature

Roosen, Alexander; Chapple, Christopher R.; Dmochowski, Roger R.; Fowler, Clare J.; Gratzke, Christian; Roehrborn, Claus G.; Stief, Christian G.; Andersson, Karl‐Erik

doi:10.1016/j.eururo.2009.07.044

Cited by 119 publications

(101 citation statements)

References 155 publications

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“…Thus animal studies have shown BoNT-A can decrease transmitter release from the urothelium (258) and neuropeptide release (193) from bladder afferents. BoNT-A does not affect the spontaneous intrinsic contractions of the detrusor (245). There is evidence that the toxin can inhibit bladder sensory pathways contributing to storage symptoms.…”

Section: Botulinum Toxinmentioning

confidence: 99%

“…Several factors may contribute to the genesis of detrusor overactivity (DO) and associated storage LUTS, including the OAB syndrome; these clearly include myogenic and neurogenic factors, but a contribution of the urothelium is also likely (14,245). Three theories, the myogenic, neurogenic, and urotheliogenic, each of which probably contributes in varying proportion to the complex mechanisms underlying the genesis of DO and the OAB syndrome, have been put forward and are discussed in detail elsewhere (245).…”

Section: Bladder Overactivitymentioning

confidence: 99%

“…Three theories, the myogenic, neurogenic, and urotheliogenic, each of which probably contributes in varying proportion to the complex mechanisms underlying the genesis of DO and the OAB syndrome, have been put forward and are discussed in detail elsewhere (245).…”

Section: Bladder Overactivitymentioning

confidence: 99%

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Urothelial Signaling

Birder

Andersson

2013

Physiological Reviews

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399

362

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The urothelium, which lines the inner surface of the renal pelvis, the ureters, and the urinary bladder, not only forms a high-resistance barrier to ion, solute and water flux, and pathogens, but also functions as an integral part of a sensory web which receives, amplifies, and transmits information about its external milieu. Urothelial cells have the ability to sense changes in their extracellular environment, and respond to chemical, mechanical and thermal stimuli by releasing various factors such as ATP, nitric oxide, and acetylcholine. They express a variety of receptors and ion channels, including P2X3 purinergic receptors, nicotinic and muscarinic receptors, and TRP channels, which all have been implicated in urothelial-neuronal interactions, and involved in signals that via components in the underlying lamina propria, such as interstitial cells, can be amplified and conveyed to nerves, detrusor muscle cells, and ultimately the central nervous system. The specialized anatomy of the urothelium and underlying structures, and the possible communication mechanisms from urothelial cells to various cell types within the bladder wall are described. Changes in the urothelium/ lamina propria ("mucosa") produced by different bladder disorders are discussed, as well as the mucosa as a target for therapeutic interventions.

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Section: Botulinum Toxinmentioning

confidence: 99%

Section: Bladder Overactivitymentioning

confidence: 99%

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Urothelial Signaling

Birder

Andersson

2013

Physiological Reviews

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399

362

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“…Moreover, it is well established that the function of the systemic renin-angiotensin system is in part regulated by β-adrenoceptors, in humans β 1 -adrenoceptors, but a local renin-angiotensin system also exists in the urogenital tract (Comiter 2012). β-Adrenoceptors are also known to affect the function of gap junctions in the heart (Salameh and Dhein 2011), and gap junctions also play a role in the regulation of bladder function (Roosen et al 2009). Moreover, adrenergic agonists can affect expression of uroplakin in the bladder, and this may play a role in cystitis (Kyung et al 2012).…”

Section: Perspectivementioning

confidence: 99%

Pharmacological profile of β3-adrenoceptor agonists in clinical development for the treatment of overactive bladder syndrome

Igawa

Michel

2012

Naunyn-Schmiedeberg's Arch Pharmacol

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β 3 -Adrenoceptor agonists are an emerging drug class for the treatment of the overactive bladder syndrome, and clinical proof-of-concept data have been obtained for three representatives of this class, mirabegron, ritobegron, and solabegron. We review here the pharmacological profile of these three drugs and discuss the potential clinical relevance of differences between them. In the absence of direct comparative studies, it appears that all three are strong agonists selective for β 3 -vs. β 1 -and β 2 -adrenoceptors in studies with cloned receptor subtypes. The potency of these agonists may be species-dependent, with all three having high potency in the human detrusor. All three agonists were effective in one or more animal models of bladder dysfunction, which typically involved reductions of micturition frequency. Agonist doses effective for bladder function lowered blood pressure in some cases, but the relevance of this for clinical use is difficult to determine due to species differences in the importance of cardiovascular β 3 -adrenoceptors. While limited effects on other organ systems are expected for β 3 -adrenoceptor agonists, this requires further investigation.

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“…An estimated 45.2% of the 2008 worldwide population (4.3 billion) was affected by at least one LUTS and, by 2018, an estimated 2.3 billion individuals will be affected (18.4% increase). It is well-known that the causes of LUTS, including OAB, are multifactorial and involve many pathophysiologic mechanisms in both men and women [Roosen et al 2009;Banakhar et al 2012;Meng et al 2012]. However, particularly in the elderly, ageing-associated changes in pelvic vasculature, such as atherosclerosis, may be an important contributing factor in both sexes [Ponholzer et al 2006].…”

Section: Introductionmentioning

confidence: 99%

Pharmacological treatment of chronic pelvic ischemia

Andersson

Nomiya

Sawada

et al. 2014

Therapeutic Advances in Urology

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Abstract:Epidemiological studies have shown that lower urinary tract symptoms, including overactive bladder, commonly occur in both men and women, with an age-related increase in both sexes. Vascular endothelial dysfunction and urological symptoms are common in the metabolic syndrome; they also occur during the human ageing process and are independent risk factors for the development of atherosclerosis and hypertension. Pelvic arterial insufficiency may lead to impaired lower urinary tract perfusion and play an important role in the development of bladder dysfunction such as detrusor overactivity and overactive bladder. It seems reasonable, but has not been definitely established clinically, that chronic ischemiarelated bladder dysfunction will progress to bladder underactivity. Studies in experimental models in rabbits and rats have shown that pelvic arterial insufficiency may result in significant bladder ischemia with reduced bladder wall oxygen tension, oxidative stress, increased muscarinic receptor activity, ultrastructural damage, and neurodegeneration. Several types of drug may be able to prevent some of these changes. Even if the α 1 -adrenoceptor blocker, silodosin, the phosphodiesterase type 5 inhibitor, tadalafil, the β 3 -α 1 -adrenoceptor agonist, mirabegron, and the free radical scavenger, melatonin, were unable to prevent the development of neointimal hyperplasia and consequent luminal occlusion in animal models, they all exerted a protecting effect on urodynamic parameters, and on the functional and morphological changes of the bladder demonstrable in vitro. The different mechanisms of action of the drugs suggest that many factors are involved in the pathogenesis of chronic ischemia-induced bladder dysfunction and can be targets for intervention. Since several of the agents tested are used clinically and effectively for relieving lower urinary tract symptoms, the results from animal models of chronic bladder ischemia seem to have translational value. Animal models may be of relevance for designing clinical studies to demonstrate if a certain drug may prevent progression of ischemia-related functional and morphological bladder changes.

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A Refocus on the Bladder as the Originator of Storage Lower Urinary Tract Symptoms: A Systematic Review of the Latest Literature

Cited by 119 publications

References 155 publications

Urothelial Signaling

Urothelial Signaling

Pharmacological profile of β3-adrenoceptor agonists in clinical development for the treatment of overactive bladder syndrome

Pharmacological treatment of chronic pelvic ischemia

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