Effects of sensory neuron-specific receptor agonist on bladder function in a rat model of cystitis induced by cyclophosphamide

Int Urol Nephrol. 2014 Oct;46(10):1953-9. doi: 10.1007/s11255-014-0734-x. Epub 2014 May 14.

Abstract

Purpose: To investigate the effects of activation of sensory neuron-specific receptors (SNSRs) on cyclophosphamide (CYP) bladder overactivity in rats.

Methods: Female Sprague-Dawley rats (235-258 g) were used. Rats were injected with either CYP (200 mg/kg, intraperitoneally) or saline (control). Continuous cystometrograms (0.04 ml/min) were recorded 48 h after CYP or saline injection under urethane anesthesia. After stable micturition cycles were established, a selective rat SNSR1 agonist, bovine adrenal medulla 8-22 (BAM8-22), was administered intravenously or intrathecally.

Results: Cyclophosphamide treatment-induced higher baseline pressure and shorter intercontraction intervals compared with the control group. Intravenous administration of BAM8-22 at 10, 30 and 100 μg/kg significantly increased intercontraction intervals in the CYP-treated group. Intrathecal administration of BAM8-22 at 0.03, 0.1 and 0.3 μg also significantly increased intercontraction intervals in the CYP-treated group. Intravenous or intrathecal administration of BAM8-22 did not change baseline pressure or maximum voiding pressure in the CYP-treated group.

Conclusions: These findings indicate that activation of SNSRs can suppress CYP-induced bladder overactivity, probably due to suppression of bladder afferent activity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cyclophosphamide / toxicity*
  • Cystitis / chemically induced*
  • Cystitis / drug therapy*
  • Disease Models, Animal
  • Female
  • Peptide Fragments / pharmacology*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Peptide Fragments
  • bovine adrenal medulla 8-22
  • Cyclophosphamide