Effects of urethane on reflex activity of lower urinary tract in decerebrate unanesthetized rats

Abstract

Effects of urethane on lower urinary tract function were examined in decerebrate unanesthetized rats. During single slow infusion (0.04 ml/min) cystometrograms (CMGs), urethane (0.3 g/kg) increased micturition pressure threshold (PT) by 73%, postvoid residual volume (RV) by 425%, and decreased voiding efficiency (VE) by 57%, but did not change maximal voiding pressure (MVP), closing peak pressure (CPP), bladder compliance, bladder contraction duration (BCD), or volume threshold (VT) for inducing micturition. Lower doses (0.01-0.1 g/kg) did not alter any parameter. During continuous fast infusion (0.21 ml/min) CMGs, urethane at doses of 0.6-1.2 g/kg (iv) markedly decreased CPP by 69-85%, whereas only the largest dose (1.2 g/kg iv) decreased MVP and external urethral sphincter electromyogram activity by 42 and by 80%, respectively. Doses of 0.001-0.6 g/kg did not alter the intercontraction interval and BCD. Taken together, these results suggest that urethral activity, which is essential for efficient voiding, is more sensitive to the suppressive effect of urethane than afferent or efferent mechanisms controlling the bladder. The threshold dose of MK-801 (0.3 mg/kg), an NMDA antagonist, required to decrease MVP and increase VT in urethane (1.2 g/kg)-anesthetized rats, only increased VT in rats treated with a subanesthetic dose of urethane (0.3 g/kg), suggesting a higher sensitivity of the afferent vs. efferent limb of the micturition reflex pathway to urethane-MK-801 interactions. Because effects of urethane persisted after removal of the forebrain, they must be mediated by actions on the brain stem, spinal cord, or peripheral nervous system.

Fig. 1.

Change of intravesical infusion rate influences closing peak pressure (CPP) during continuous cystometrograms (CMGs). Solid lines and broken lines indicate the period of fast-infusion cystometry (0.21 ml/min) and slow-infusion cystometry (0.04 ml/min), respectively. Note that CPPs during CMGs at an infusion rate of 0.21 ml/min are markedly higher than those at an infusion rate of 0.04 ml/min. MVP, maximal voiding pressure.

Fig. 2.

Effects of urethane (0.01 and 0.3 g/kg iv) and subsequent MK-801 (0.3 mg/kg iv) administration on bladder activity during single CMGs (0.04 ml/min). Note that urethane doses change neither MVP nor volume threshold for inducing micturition (VT) and that MK-801 (0.3 mg/kg) after urethane at a cumulative dose of 0.3 g/kg markedly increased VT but did not alter MVP. “Basal” is defined as before urethane administration. Arrows indicate the start of intravesical infusion.

Fig. 3.

Graphs showing effects of urethane in a cumulative dosing manner (0.01–0.3 g/kg iv) on CMG parameters during single-infusion CMGs (0.04 ml/min; n = 10). PT, pressure threshold for inducing micturition contraction; BCP, bladder compliance; BCD, bladder contraction duration; VV, voided volume; RV, postvoiding residual volume; VE, voiding efficiency. Statistical differences from baseline (BL) are *P < 0.05, **P < 0.01, ***P < 0.001 (by Dunn's multiple comparison test after a Friedman test).

Fig. 4.

Effects of urethane in a cumulative dosing manner (0.03–1.2 g/kg iv) on bladder and external urethral sphincter (EUS) electromyogram (EMG) activity during continuous-infusion CMGs (0.21 ml/min). Recordings were obtained 5–10 min after the administration of the drug indicated above each record. Note that bladder contraction pressure and concomitant EUS EMG activity are suppressed by increasing doses of urethane and are abolished by the 1.2 g/kg dose of urethane. pps, Pulses per second.

Fig. 5.

Graphs showing effects of urethane in a cumulative dosing manner (0.001–1.2 g/kg iv) on cystometric parameters during continuous-infusion CMGs (0.21 ml/min; n = 5). ICI, intercontraction interval. Because urethane doses at 0.9 g/kg blocked the reflex bladder contractions in 2 rats and 1.2 g/kg abolished bladder activity in an additional rat, statistical evaluations for BCD and ICI were not made at these doses. Statistical differences from basal conditions (bl) are *P < 0.05, **P < 0.01, ***P < 0.001 (by Dunn's multiple comparison test after a Friedman test).