Supraspinal N-methyl-D-aspartate receptor inhibition influences the micturition reflex and function of the upper urinary tract of anesthetized and conscious rats

Aims: To examine the effects of N-methyl-D-aspartate (NMDA) receptor antagonists on the frequency/volume (F/V) characteristics of micturition of conscious and anesthetized rats in relation to the mechanisms of renal urine output and pyelo-ureteral transport function of the upper urinary tract. Methods: Micturition F/V characteristics of 24 conscious female Sprague-Dawley rats, each weighting 160-180 g, were evaluated in a metabolic chamber. Control values of (F/V) were first obtained after administration of a 5-mL loading dose of saline solution and compared with intraperitoneal (i.p.) injection of 0.3 - 6.0 mg/kg of LY274614 (LY) and 0.3 - 40 mg/kg of dextromethorphan (DEX). Upper urinary tract studies were performed on two groups of urethane anesthetized rats (1.2 g/kg, s.c.). A group of 17 rats was used for intravenous (i.v.) injection of 1-30 mg/kg of LY and 1-10 mg/kg of DEX. In a second group of 12 rats, 0.2 mg/kg of LY and DEX were administered intracerebroventricularly (i.c.v.), by placing a catheter into the third ventricle. In anesthetized rats, continuous cystometrograms (CMG) were done while perfusing the renal pelvis with indigo carmine, and measuring pelvic and arterial pressure and as well as visualizing the transport of urine within the upper urinary tract by using videomicroscopic imaging. Results: In conscious rats, the i.p. injection of LY and DEX produced a significant and dose-dependent increase in functional bladder capacity and a considerable increase in diuresis. In anesthetized rats, i.v. and i.c.v. administration of LY and DEX affected the micturition reflex, reflected as a significant increase in bladder capacity and preleakage pressure. Videomicroscopic imaging shows dilation of the ureter and a dilution of the dyed urine after the i.v. and i.c.v. injection of LY and DEX. The frequency of ureteral peristalsis and renal pelvic contractions were significantly decreased after i.v. and i.c.v. injection of LY as well as DEX. Conclusions: The present study shows that the NMDA receptor antagonists LY and DEX given systemically (i.v. and i.p.) or intracerebroventricularly influence the micturition reflex and modulate pyelo-ureteral motility as well as the rate of urine production. From the present study, it is suggested that NMDA receptors are directly involved in regulating pyelo-ureteral peristalsis as well as in the coordination of urine transport between upper and lower urinary tract. Neurourol Urodynam. 22:164-175, 2003. (C) 2003 Wiley-Liss, Inc.