Acute unilateral ureteral distension inhibits glutamate-dependent spinal pelvic-urethra reflex potentiation via GABAergic neurotransmission in anesthetized rats

Abstract

The effects of an acute increase in intraureteral pressure (IUP) on pelvic-urethra reflex potentiation were examined in urethane-anesthetized rats by recording the external urethral sphincter electromyogram activities evoked by the pelvic afferent stimulation. Compared with a single action potential elicited by the test stimulation (TS; characterized by an intensity that evoked a constant reflex response without facilitation, 1/30 Hz, 1.03 +/- 0.12 spikes/stimulation, n = 7), the repetitive stimulation [RS; identical stimulation intensity as the TS (1 Hz)] significantly induced spinal reflex potentiation (SRP; 16.90 +/- 2.00 spikes/stimulation, P < 0.01, n = 7). Such SRP was significantly attenuated by intrathecal 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo (F) quinoxaline [NBQX; a glutamatergic alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionat (AMPA) receptor antagonist] and d-2-amino-5-phosphonovalerate [APV; a glutamatergic N-methyl-d-aspartate (NMDA) antagonist; the spike number per stimulation: 11.0 +/- 0.70 for NBQX, 1.01 +/- 0.30 for APV, and 16.90 +/- 2.0 for RS, respectively, n = 7, P < 0.01]. Acute stepwise elevations of IUP gradually attenuated and eventually abolished the RS-induced SRP (16.80 +/- 1.30, 17.00 +/- 1.30, 16.30 +/- 1.30, 10.50 +/- 1.80, 8.80 +/- 1.90, 3.50 +/- 1.60, 0.80 +/- 0.20, 0.70 +/- 0.20, and 0.20 +/- 0.10 spikes/stimulation at intraureteral pressure of 0, 2.5, 5, 7.5, 10, 12.5, 15, 17.5, and 20 cmH(2)O, respectively, n = 7). Intrathecal NMDA (a glutamatergic NMDA receptor agonist) and bicuculline (a GABA receptor antagonist) both reversed the abolition of RS-induced SRP caused by unilateral ureteral distension (14.0 +/- 4.04 and 8.00 +/- 1.53 spikes/stimulation, respectively, n = 7, P < 0.01). All the results suggested unilateral ureteral distension might compensatorily relax the urethra via GABAergic inhibition of NMDA-dependent SRP.