Changes in Angiotensin II Type 1 Receptor Expression in the Rat Bladder by Bladder Outlet Obstruction

Abstract

Purpose: To demonstrate the change in the expression of angiotensin II type 1 receptor (AT1) in the rat bladder with partial bladder outlet obstruction (P-BOO). Materials and Methods: Bladder specimens were obtained from 12-week-old Wistar female rats that were divided into two groups, a P-BOO group and a control group. The rats of the P-BOO group were divided into six groups: a sham-operated control group, 1 day postoperatively, 2 days postoperatively, 4 days postoperatively, 7 days postoperatively and 14 days postoperatively. The cystometric findings and immunohistochemical staining of the detrusor muscle with the AT1 antibody were compared in each group. Results: AT1 localized on the cell membrane of the detrusor smooth muscle and in cytoplasm of suburothelial myofibroblasts in the control rats. The expression of AT1 disappeared in the detrusor muscle and suburothelial myofibroblasts in P-BOO, but AT1 was highly expressed in urothelial cells 1 day after surgery. The expression of AT1 in urothelial cells gradually decreased with time after surgery. AT1 completely disappeared in urothelial cells 14 days after surgery. Conclusions: The present study demonstrated that the site of AT1 expression changes in response to the mechanical stress caused by P-BOO, and finally there was no expression of AT1 in rat bladder tissue following P-BOO. These data suggest the change in AT1 expression may play a role in bladder function.

Activation of common signaling pathways during remodeling of the heart and the bladder

“…The heart contains a local RAS system, which is activated by pressure overload [124], and blocking Ang II formation with angiotensin converting enzyme inhibitors attenuates pressure overload-mediated heart hypertrophy in animals and humans [125]. Ang II stimulates AT1 receptors which are expressed in the bladder in both smooth muscle and urothelial cells, and Ang II-mediated detrusor contractility has been reported [126]. Application of AT1 receptor antagonists in animal models of pBOO significantly reduced organ hypertrophy and collagen deposition, implicating activation of RAS in bladder fibrosis [127].…”

Chronic Urinary Retention Could Decrease the Number of Suburothelial Myofibroblasts in the Rat Bladder

“…We previously reported that AT1 is expressed on suburothelial myofibroblasts [9]. Therefore, we must confirm the changes in the number of suburothelial myofibroblasts induced by the administration of angiotensin receptor blockade in CUR rats in the future.…”

“…Previously, our group demonstrated that angiotensin receptors are expressed on suburothelial myofibroblasts [9]. Yamada et al [10] reported that angiotensin II type 1 receptors (AT1) are decreased in the bladders of partial bladder outlet obstruction (P-BOO) rats.…”

Age‐related changes in bladder function with altered angiotensin II receptor mechanisms in rats

“…It has recently been reported that telmisartan, an AT1 receptor antagonist, suppresses detrusor overactivity in association with reduced expression of AT1 receptors in the bladder from rats with partial bladder outlet obstruction (P‐BOO) . We also reported that AT1 receptors are highly expressed in the bladder mucosa of P‐BOO rats, and that the expression of AT1 receptors and gap junctional protein connexin43 (Cx43) was increased in the bladder submucosa of rats with HCl‐induced bladder inflammation . The AT1 receptor is known to induce interstitial fibrosis and also activation of ERK1/2 MAP kinase (ERK1/2) leading to an increase in Cx43 expression, which is considered as a cause of overactive bladder (OAB) .…”