Experimental study of 5-hydroxytryptamine 1A receptor agonist to improve the voiding dysfunction in diabetic rats

Abstract

Objective To investigate the effect of 5-hydroxytryptamine 1A (5-HT1A) receptor agonists to improve micturition function in rats with diabetes mellitus (DM).Methods Fourteen female SD rats with the weight of 250 to 275 g were used.Seven rats were in the DM model group with intraperitoneal injection streptozotocin (STZ,65 mg/kg).Rats in the control group and DM group were anesthetized with urethane (1.3 g/kg) 8 weeks later.A polyethylene (PE)-50 catheter were placed in the left jugular vein for intravenous drug administration.A PE-90 catheter was inserted into the bladder,with the other end connected to a syringe pump for continuous infusion of saline and a pressure transducer for intravesical pressure monitor.Dose-response curves for 8-OH-DPAT were followed by WAY-100635 test.The capacity,residual volume,micturition volume,and EUS-EMG were measured.Results Compared to normal control,DM rats had a higher bladder capacity,residual volume,and a lower voiding efficiency.With increasing dose of 8-OH-DPAT (0.003-1.000 mg/kg,i.v.),the micturition volume increased from (2.15±0.49) ml to (2.85±0.21) ml,the residual volume decreased from (3.40±0.74)ml to (1.82±0.48) ml and voiding efficiency changed from (39.0±9.3)％ to (61.6±6.9)％.Control rats showed little change in cystometic variable.During the micturition,there was a dose-dependent increased phasic EUS activity correlated with the improved voiding efficiency.WAY-100635 (0.300 mg/kg,i.v.) reversed the 8-OH-DPAT-induced changes.Conclusions Both the bladder voiding efficiency and the periodic EUS activity decrease in DM rats.5-HT1A receptor agonist could promote periodic EUS activity and improve voiding efficiency. Key words: Rats; Diabetes mellitus; Micturition; Receptor, serotonin, 5-HT1A; Serotonin agonists