title: Short-term modulation of distal tubule fluid nitric oxide in vivo by loop NaCl reabsorption.
abstract: BACKGROUND
  Intrarenal nitric oxide (NO) production and signaling effects are influenced by NaCl loading. To gain further insight into NO mechanisms we determined whether rat distal tubular fluid (DTF) [NO] and collected NO may acutely change when NaCl loop delivery is altered.
  
  
  METHODS
  An NO microelectrode was used to measure real-time DTF [NO] and DT-collected NO. With proximal flow blocked (open system), 150 mmol/L NaCl, with and without 10(-4) mol/L furosemide was perfused with measurement of loop [Cl] reabsorption. Using a closed system, DTF [NO] was also determined using several different loop perfusates.
  
  
  RESULTS
  In the open system, perfusion with 40 nL/min of 150 mmol/L NaCl to which 10(-4) mol/L furosemide was added, DT [NO] and DT-collected NO was approximately twice that measured with perfusion of 150 mmol/L NaCl alone, while loop Cl reabsorption decreased by half. In the closed system, perfusion at 10 nL/min of 150 mmol/L NaCl + furosemide 10(-4) mol/L also induced a significant rise in DTF [NO] and collected NO. Perfusion of 10(-3) mol/L S-methyl-L-thiocitrulline (SMTC) with 150 mmol/L NaCl, induces a significant drop in DT [NO], but without a significant increase in collected NO. Furthermore, with addition of 10(-3) mol/L SMTC to the 150 mmol/L NaCl + 10(-4) furosemide perfusate, the rise in DT [NO] was prevented. Analysis of covariance showed that flow changes within, or between all groups, had no significant additional effect.
  
  
  CONCLUSIONS
  In both open and closed loop perfusion systems, 10(-4) mol/L furosemide inhibition of NaCl transport stimulates net loop NO emission independent of flow; 10(-3) mol/L SMTC + 150 mmol/L NaCl reduces DT [NO], but not DT-collected NO. Short-term net NO emission from the entire loop, as collected in distal tubule fluid, increases with inhibition of loop NaCl transport.
authors.affiliation: Division of Nephrology, The Kidney Research Centre, Ottawa Health Research Institute, Ottawa, Ontario, Canada. dzlevine@ottawahospital.on.ca
authors.forename: David Z
authors.initials: DZ
authors.lastname: Levine
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Burns
authors.forename: James
authors.initials: J
authors.lastname: Jaffey
authors.forename: Michelle
authors.initials: M
authors.lastname: Iacovitti
mesh_terms: D000042:Absorption; D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D004232:Diuretics / Q000494:pharmacology; D005665:Furosemide / Q000494:pharmacology; D007686:Kidney Tubules, Distal / Q000378:metabolism*; D008297:Male; D008839:Microelectrodes; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000493:pharmacokinetics*
chemical_list: D004232:Diuretics; D009569:Nitric Oxide; D012965:Sodium Chloride; D005665:Furosemide