Type 4 phosphodiesterase inhibitor suppresses experimental bladder inflammation.
OBJECTIVE
To evaluate the effects of orally administered YM976, a specific inhibitor of type 4 phosphodiesterase (PDE4), on bladder activity in a rat model with hydrochloric acid (HCl)-induced cystitis (IC), hypothesizing that a PDE4 inhibitor might suppress bladder overactivity and bladder pain responses in bladder-hypersensitive disorders such as IC.


METHODS
Wistar rats with HCl-induced IC were treated with YM976 or vehicle and their voiding observed and assessed by cystometry. The severity of bladder inflammation (BI) was quantified using the BI index (BII), which comprises three factors (oedema, leukocyte infiltration and haemorrhage). Nociceptive neural activity was also examined using an immunohistochemical study of spinal c-fos expression.


RESULTS
YM976 significantly reduced the number of voids, and the volume per void was significantly higher than in control (vehicle) group. Cystometry showed a significant increase in bladder capacity, voided volume and voiding efficiency, and a decrease in the amplitude of voiding pressure in rats treated with YM976. All BII scores were significantly lower in the YM976 than in the control group. c-fos expression in the spine was less in the YM976 than in the control group.


CONCLUSIONS
Oral administration of YM976 significantly improved the voiding behaviour and histological damage in rats with IC induced by HCl. These results indicate that PDE4 inhibitor might be effective in relieving bladder symptoms with IC.
Kitta
Takeya
T
Department of Urology, Hokkaido University, Graduate School of Medicine, Sapporo, Japan. kitta@fb3.so-net.ne.jp
Tanaka
Hiroshi
H
Mitsui
Takahiko
T
Moriya
Kimihiko
K
Nonomura
Katsuya
K
D000818:Animals; D018856:Cystitis, Interstitial / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006851:Hydrochloric Acid / Q000008:administration & dosage; D058988:Phosphodiesterase 4 Inhibitors; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D011744:Pyrimidinones / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D053201:Urinary Bladder, Overactive / Q000188:drug therapy* / Q000473:pathology; D014563:Urodynamics / Q000187:drug effects* / Q000502:physiology
D058988:Phosphodiesterase 4 Inhibitors; D010726:Phosphodiesterase Inhibitors; D011725:Pyridines; D011744:Pyrimidinones; C414544:YM 976; D006851:Hydrochloric Acid