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Serotonin (5‐HT)2A/2C receptor agonist (2,5‐dimethoxy‐4‐idophenyl)‐2‐aminopropane hydrochloride (DOI) improves voiding efficiency in the diabetic rat
Author(s) -
Tu Hongjian,
Cao Nailong,
Gu Baojun,
Si Jiemin,
Chen Zhong,
Andersson KarlErik
Publication year - 2015
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1111/bju.12684
Subject(s) - agonist , urination , ketanserin , endocrinology , medicine , chemistry , 5 ht receptor , streptozotocin , serotonin , antagonist , urology , receptor , diabetes mellitus , urinary system
Objectives To examine the effects of the serotonin (5‐ HT ) 2A/2C receptor agonist (2,5‐dimethoxy‐4‐idophenyl)‐2‐aminopropane hydrochloride ( DOI ) on micturition in rats with diabetes mellitus ( DM ). Methods Female S prague– D awley rats ( n = 16) were divided into two groups: rats with Type 1 DM and age‐matched control rats. DM was induced by i.p. injection of streptozotocin (65 mg/kg) and detailed cystometrogram ( CMG ) studies were performed 8 weeks post‐injection in all rats under urethane anaesthesia. The selective 5‐ HT2A antagonist ketanserin was administered after each DOI dose–response curve was plotted. All drugs were administered i.v. Results Compared with controls, comprehensive urodynamic studies showed that DM rats had a higher bladder capacity and post‐void residual urine volume ( PVR ), and a markedly lower voiding efficiency. In DM rats, DOI (0.01–0.3 mg/kg) induced significant dose‐dependent increases in micturition volume and reductions in PVR , resulting in greater voiding efficiency. CMG measurements showed a dose‐dependent increase in high‐frequency oscillation ( HFO ) activity, evidenced by an increased duration of HFO s per voiding. This correlated with the improved voiding efficiency. Ketanserin (0.1 mg/kg) partially or completely reversed the DOI ‐induced changes. Conclusions The HFO s observed in the present study seem to correlate with external urethral sphincter bursting activity during voiding. Bladder voiding efficiency was reduced in DM rats. The 5‐ HT2A receptor agonist can enhance HFO activity and improves voiding efficiency, and so may represent a new strategy to improve voiding efficiency after DM in experimental studies.