Effect of the Renin‐Angiotensin System on the Obstructed Bladder

Abstract

Bladder hypertrophy and dysfunction are well-known bladder responses to outlet obstruction (i.e. urodynamic overload). Cardiac hypertrophy and heart failure are also caused by hemodynamic overload, and many basic and clinical studies suggest that the local renin-angiotensin system (RAS) has a crucial role in load-induced cardiac pathogenesis. The similarity of the response of the heart and the bladder to overload suggests that angiotensin II (AngII) may have a similar regulatory role in pathological remodeling, such as muscle growth and collagen production of the obstructed bladder. Previous in vitro studies show that angiotensin I is converted to AngII by angiotensin converting enzyme (ACE) or chymase, which exists in the human bladder. In addition, many studies using contractile responses to AngII, autoradiography, radioreceptor assay and mRNA expression demonstrate the presence of AngII receptor in the bladder from various animals and the human. Recent evidence indicates that AngII is released from bladder smooth muscle cells (SMCs) in response to a repetitive stretch stimulus, and subsequently activates AT1 in an autocrine fashion. This AT1 activation has been shown to mediate heparin-binding epidermal growth factor-like growth factor gene expression and to increase the DNA synthesis rate of bladder SMCs. Consistent with this in vitro study, previous studies and our preliminary data suggest the usefulness of AT1 antagonists or ACE inhibitor in bladder outlet obstruction of the rabbit and rat. Taken together, the local RAS contributes to structural and functional alterations in the bladder after obstruction.Key words angiotensin converting enzyme inhibitor, angiotensin II type 1 receptor antagonist, bladder hypertrophy, bladder outlet obstruction, renin angiotensin system

Blueberry Prevents the Bladder Dysfunction in Bladder Outlet Obstruction Rats by Attenuating Oxidative Stress and Suppressing Bladder Remodeling

“…In previous reports, Wiseman et al reported that flavonoid-rich blueberries could inhibit angiotensin-converting enzyme activity [29]. Also, Aikawa et al reported that angiotensin receptor blockers prevented the development of DO in BOO rats [30]. These results indicate that the administration of angiotensin receptor blockers significantly suppressed bladder weight increase and bladder smooth muscle layer fibrosis in BOO rats.…”

Editorial comment Re: Elliott CS, Comiter CV. The effect of angiotensin inhibition on urinary incontinence: Data from the National Health and Nutrition Examination Survey (2001–2008). Neurourol urodyn 2014; 33:1178–81

“…Consequently, this opens perspectives to use inhibitors of the angiotensin II activity in the clinical management of some urologic disorders . Angiotensin II is also a local trophic factor that is involved in the development of load‐induced bladder hypertrophy, for example, in patients with bladder outlet obstruction . Furthermore, sex hormones also seem to influence the local RAS in the bladder, as recently published by Nakazawa et al In their experiments on rats, they observed a correlation between androgen status and expression of AT2 receptors (angiotensin II receptor type 2) and apoptosis‐related proteins in the bladder.…”

“…Local RAS in the bladder enhances detrusor contractions through the action of angiotensin II . Consequently, this opens perspectives to use inhibitors of the angiotensin II activity in the clinical management of some urologic disorders .…”

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“…The obtained results indicate a small number of studies on this topic [4,13]. Basically, in the majority of scientific works, stem cells were used for the purpose of tissue engineering [2,14], the effect of increased contractility of UB and endogenous NFs, growth factors on the morphology and function of the urinary tract [12,[15][16][17][18], the effect of high hydrostatic pressure on different cell cultures [19], the role of NFs in neurodegenerative diseases [5,20]. The increased interest in this topic was caused by the results we obtained in previous works.…”