Effect of bilateral hypogastric nerve transection on voiding dysfunction in rats with spinal cord injury.
We determined if bilateral section of the hypogastric nerves (HGN), which provide the major sympathetic input to the urinary bladder neck/proximal urethra, could improve voiding by reducing urethral resistance in conscious, female spinal-cord-injured (SCI) rats 2-3 weeks after T(7-9) transection of the spinal cord. Cystometry was performed in animals with HGN intact and with HGN sectioned bilaterally 1-2 h before the experiment. Residual volume (RV), volume threshold for inducing micturition (VT), maximal voiding pressure, and bladder compliance were significantly lower (71, 35, 33, and 31%, respectively) in SCI rats with sectioned HGN than in rats with intact HGN, whereas voided volume (VV), pressure threshold for micturition, and bladder contraction duration (BCD) in the two groups were similar. Voiding efficiency (VE) in the HGN-sectioned group was 36% greater than that in the HGN-intact group. Antagonists for AMPA and NMDA glutamatergic receptors (LY215490 and MK-801, respectively) were administered to rats with sectioned HGN, to determine if activity in the HGN contributes to the previously reported inhibitory effects of these drugs, on voiding function after SCI. MK-801 (3 mg/kg iv) significantly reduced VV (75%) and VE (85%) and increased RV (8-fold), VT (87%), and bladder compliance (60%), whereas LY215490 (10 mg/kg iv) significantly increased VT and BCD by 15 and 19%, respectively. It is concluded that bilateral section of HGN reduces voiding dysfunction in the SCI rat but does not alter the effects of AMPA and/or NMDA glutamatergic receptor antagonists on the micturition reflex in the SCI rat. Thus the effects of these drugs are not dependent on changes in activity of sympathetic axons in the HGN.
Yoshiyama
Mitsuharu
M
Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. PXN15164@nifty.ne.jp
de Groat
William C
WC
D000818:Animals; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004359:Drug Therapy, Combination; D005260:Female; D007546:Isoquinolines / Q000494:pharmacology; D009119:Muscle Contraction; D018696:Neuroprotective Agents / Q000494:pharmacology; D010525:Peripheral Nerves / Q000601:surgery*; D051381:Rats; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D013119:Spinal Cord Injuries / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D013562:Sympathectomy / Q000379:methods; D013777:Tetrazoles / Q000494:pharmacology; D016896:Treatment Outcome; D014554:Urination / Q000187:drug effects; D014555:Urination Disorders / Q000209:etiology / Q000503:physiopathology* / Q000601:surgery*; D014556:Urine / Q000502:physiology
D007546:Isoquinolines; D018696:Neuroprotective Agents; D018091:Receptors, AMPA; D013777:Tetrazoles; D016291:Dizocilpine Maleate; C082309:tezampanel