title: The link between vascular dysfunction, bladder ischemia, and aging bladder dysfunction.
abstract: The vascular supply to the human bladder is derived mainly from the superior and inferior vesical arteries, the latter being directly connected to the internal iliac artery. Aging is associated with an impairment of blood vessel function and changes may occur in the vasculature at the molecular, cellular and functional level. Pelvic arterial insufficiency may play an important role in the development of bladder dysfunctions such as detrusor overactivity (DO) and the overactive bladder syndrome. Chronic ischemia-related bladder dysfunction may progress to bladder underactivity and it would be desirable to treat not only lower urinary tract symptoms (LUTS) induced by chronic ischemia, but also the progression of the morphological bladder changes. 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. In turn, this will lead to oxidative stress associated with upregulation of oxidative stress-sensitive genes, increased muscarinic receptor activity, ultrastructural damage, and neurodegeneration. The phosphodiesterase type 5 (PDE5) inhibitor tadalafil, the α1-adrenoceptor (AR) blocker silodosin, the β3-AR agonist mirabegron, and the free radical scavenger melatonin, exerted a protecting effect on urodynamic parameters, and on functional and morphological changes of the bladder demonstrablein vitro. Since the agents tested are used clinically for relieving LUTS, the results from the animal models seem to have translational value, and may be of relevance for designing clinical studies to demonstrate if the drugs may prevent progression of ischemia-related functional and morphological bladder changes.
authors.affiliation: Institute of Clinical Medicine, Department of Obstetrics and Gynecology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, DK 8200 Aarhus N, Denmark.
authors.forename: Karl-Erik
authors.initials: KE
authors.lastname: Andersson
authors.affiliation: Department of Biomedicine, Aarhus University, Denmark.
authors.forename: Donna B
authors.initials: DB
authors.lastname: Boedtkjer
authors.affiliation: Department of Gynecology and Obstetrics, Aarhus University Hospital, Denmark.
authors.forename: Axel
authors.initials: A
authors.lastname: Forman
keywords: LUTS; aging; bladder blood flow; bladder dysfunction; ischemia; pharmacological treatment