The effect of angiotensin II type 1 receptor antagonist on obstructed rat bladder

2007 Fiscal Year Final Research Report Summary

• Project/Area Number: 18591762
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Urology
• Research Institution: Fukushima Medical University
• Principal Investigator: AIKAWA Ken Fukushima Medical University, School of Medicine, Assistant professor (80295419)
• Project Period (FY): 2006 – 2007
• Keywords: bladder / obstruction / rat / angiotensin II / receptor / antagonist / blood flow / function

Research Abstract

The present study aimed to explore the effect of the angiotensin II type 1 receptor antagonist, candesartan, on some of the consequences of bladder outlet obstruction (BOO). e. g. hypertrophy. fibrosis and loss of contractile function, as candesartan inhibits cardiovascular smooth muscle cell growth and fibrosis in vitro or in vivo. In 20 male SD rats (12 Weeks old). BOO was produced by a standardized method; two weeks later, one group received subcutaneously candesartan (0.2mg/kg/day) by means of osmotic pump for 4 weeks (candesartan group)and the remaining rats received vehicle (BOO group). Sham-operated rats (N=10) were used as controls (sham group). Each rat was assessed by bladder blood flow, bladder weight, histology and bladder strip contractility. There was no significant difference with bladder blood now among 3 groups. There was a significant increase in bladder weight in the BOO group compared to sham group. However, candesartan treatment significantly inhibited the bladder weight. Using Elastica-Masson stain, the area of collagen fibers within the bladder smooth muscle layer was significantly increased in BOO group compared to sham group. Candesartan treatment significantly inhibited the increased fibrosis in bladder muscle layer. There was no significant difference with the area of muscle fibers among 3 groups. BOO resulted in significant decreased contractile responses to electrical-field stimulation. carbachol and KCI. Candesartan treatment resulted in significant increased contractile responses to elecirical-field stimulation, carbachol and KCI compared to BOO group. The angiotensin II type 1 receptor antagonist, candesartan, prevented bladder fibrosis. and appeared to reduce some of the negative functional changes of the bladder smooth muscle. which occurs with BOO-induced increases in bladder weight.