Effects and mechanisms of phosphodiesterase type 5 inhibitors on rats with overactive bladder

Department of Urology, Wenzhou Medical College, Wenzhou, China.

 

OBJECTIVE: To investigate the effects and the possible mechanistic pathway of phosphodiesterase type 5 (PDE5) inhibitors on rats with overactive bladder.

METHODS: A total of 24 adult male spontaneously hypertensive rats (SHRs) were randomly divided into 3 groups: daily lavage group, discontinuous lavage group and blank group (n = 8 each). Daily vardenafil (10 mg×kg(-1)×d(-1)), discontinuous vardenafil (10 mg×kg(-1)×d(-1)) and daily normal saline were administered respectively to 3 groups by lavage. And 8 adult male SD rats were included into the control group. Bladder urodynamic examinations were conducted in each group 2 weeks later. Then bladder detrusor muscle strips isolated from each group were further divided into two parts. One part was first pre-contracted and then the relaxant effects of sodium nitroprusside and Y-27632 were observed. For another part, enzyme-linked immunosorbent assay was used to measure cyclic guanosine monophosphate (cGMP).

RESULTS: As compared with the control group, the values of bladder intercontraction interval (ICI) and bladder capacity (BC) were significantly lower [(409 ± 36) s vs (568 ± 60) s, (284 ± 25) µl vs (395 ± 42) µl, P < 0.01] while the bladder nonvoiding contraction (NVC) was significantly higher in the blank group [(2.03 ± 0.49) number/min vs(1.07 ± 0.30) number/min, P < 0.01]. Compared with the blank group, the values of ICI and BC were elevated. NVC decreased obviously in the discontinues and daily lavage groups [(486 ± 53) s and (564 ± 44) s; (337 ± 37) µl and (392 ± 30) µl; (1.82 ± 0.32) number/min and (0.52 ± 0.23) number/min, P < 0.05]. The effects were more significant in the daily lavage group (P < 0.01). The maximal relaxant effect of sodium nitroprusside was obviously enhanced in the discontinues and daily lavage groups [(50.6 ± 2.1)% and (67.9 ± 4.1)% vs(25.3 ± 5.0)%, P < 0.01]. However the sensitivity of Y-27632 decreased significantly [(35.8 ± 2.5)% and (20.2 ± 2.3)% vs (71.6 ± 2.8)%, P < 0.01], while the level of cGMP was significantly higher in the bladder detrusor muscle [(20.6 ± 4.1) fmol/mg and (29.4 ± 4.3) fmol/mg vs (12.9 ± 2.1) fmol/mg, P < 0.01]. The effects of the daily lavage group were more pronounced (P < 0.01).

CONCLUSION: The phenomenon of bladder overactivity is observed in the SHRs. The PDE5 inhibitors are effective in treating overactive bladder. And the effect of daily supplement is much better. In addition, the mechanism may operate through the cGMP-dependent protein kinase G-RhoA/Rho kinase signaling pathway.

Written by:
Chen HD, Ye XT, Weng ZL, Li CD.   Are you the author?

Reference: Zhonghua Yi Xue Za Zhi. 2011 Jul 26;91(28):2001-5.

PubMed Abstract
PMID: 22093899

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