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.