title: Nitric oxide metabolites in the lumbosacral spinal cord interstice and cerebrospinal fluid in female rats with acute cyclophosphamide-induced cystitis. An in vivo microdialysis study.
abstract: OBJECTIVE
  To determine the concentration of nitrate/nitrite in the cerebrospinal fluid and in the dorsal horn interstice of the L6-S1 spinal cord boundary in rats with or without cystitis induced by cyclophosphamide.
  
  
  METHODS
  All experiments were conducted using Wistar female rats. A microdialysis probe was implanted in the subarachnoid space or in the spinal cord tissue at the L6-S1 segments (confirmed histologically). Two days later, the microdialysis probe was perfused with artificial cerebrospinal fluid, containing or not NG-monomethyl-L-arginine. Samples were collected every 15 minutes and kept at -20ºC. Nitrite/nitrate concentrations were determined by chemiluminescence.
  
  
  RESULTS
  In normal animals, the mean values of nitrite/nitrate concentrations in the first microdialysate sample of the cerebrospinal fluid and of the spinal cord interstice were similar (482.5±90.2pmol/75µL, n=20, and 505.7±11.5pmol/75µL, n=6, respectively), whereas, in the samples from rats with cystitis, these values were significantly greater (955.5±66.3pmol/75µL, n=8, and 926.5±131.7pmol/75µL, n=11, respectively). In both groups, NG-monomethyl-L- arginine caused a significant reduction in the nitrite/nitrate concentration. Interestingly, the maximal reduction of nitrite/nitrate concentration caused by NG-monomethyl-L- arginine was no greater than 30% of the initial values.
  
  
  CONCLUSIONS
  These results constitute the first demonstration that nitrite/nitrate concentrations in the cerebrospinal fluid and spinal cord interstice are elevated between 20- and 22 hours after cyclophosphamide-induced cystitis, and indicate that cystitis is associated with changes in the production of nitric oxide in the spinal cord segments, where most primary bladder afferents end.
authors.affiliation: Universidade de São Paulo, Ribeirão Preto, SP, Brasil.
authors.forename: Jeova Nina
authors.initials: JN
authors.lastname: Rocha
authors.forename: Gustavo
authors.initials: G
authors.lastname: Ballejo
authors.forename: Gustavo B
authors.initials: GB
authors.lastname: Oliveira
mesh_terms: D000818:Animals; D003520:Cyclophosphamide; D003556:Cystitis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D005260:Female; D008161:Lumbosacral Region; D049449:Luminescence; D017551:Microdialysis; D009566:Nitrates / Q000134:cerebrospinal fluid / Q000378:metabolism; D009569:Nitric Oxide / Q000134:cerebrospinal fluid / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009573:Nitrites / Q000134:cerebrospinal fluid / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D013116:Spinal Cord / Q000737:chemistry* / Q000378:metabolism; D013997:Time Factors; D001743:Urinary Bladder / Q000378:metabolism / Q000473:pathology; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D009566:Nitrates; D009573:Nitrites; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D003520:Cyclophosphamide; D019001:Nitric Oxide Synthase