The link between vascular dysfunction, bladder ischemia, and aging bladder dysfunction

Abstract

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 α 1 -adrenoceptor (AR) blocker silodosin, the β 3 -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 demonstrable in 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.

Role of capillary pericytes in the integration of spontaneous Ca2+ transients in the suburothelial microvasculature in situ of the mouse bladder

“…; Andersson et al . ). The beneficial effects of α‐adrenoceptor antagonists, β3‐adrenoceptor agonists or PDE5 inhibitors on bladder storage symptoms may be attributed to an improvement of the bladder microcirculation.…”

Potential vascular mechanisms in an ex vivo functional pig bladder model

“…However, prolonged or chronic ischemia may overwhelm this mechanism and, overtime, progresses to the detrusor overactivity and ultimately to detrusor underactivity observed in diseases of chronic ischemia. 2,23 We propose that this present study may characterize an initial acute stage in the spectrum of progression to DU.…”

“…Nearly 50% of men and women undergoing urodynamics for lower urinary tract symptoms (LUTS) have been found to have detrusor underactivity, with increasing prevalence associated with increasing age . Chronic ischemia is a recognized risk factor in the pathophysiology of this disease process in the pre‐clinical and clinical settings . Decreased bladder perfusion is known to occur at higher fill volumes or pressures, but whether repetitive cyclic episodes of relative ischemia can lead to the pathophysiology of UAB remains to be determined.…”

“…Chronic ischemia is a recognized risk factor in the pathophysiology of this disease process in the pre‐clinical and clinical settings . Decreased bladder perfusion is known to occur at higher fill volumes or pressures, but whether repetitive cyclic episodes of relative ischemia can lead to the pathophysiology of UAB remains to be determined.…”

Is bladder blood flow an etiologic factor for the bladder pain syndrome?

“…At a rat study, Saito et al reported that bladder blood flow was significantly lower in older rats compared with the younger rats. Vascular stiffness increased and vascular compliance decreased with aging . These morphological changes may also cause vascular insufficiency and lead to organ dysfunction.…”