Short-term modulation of distal tubule fluid nitric oxide in vivo by loop NaCl reabsorption.
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.
Levine
David Z
DZ
Division of Nephrology, The Kidney Research Centre, Ottawa Health Research Institute, Ottawa, Ontario, Canada. dzlevine@ottawahospital.on.ca
Burns
Kevin D
KD
Jaffey
James
J
Iacovitti
Michelle
M
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*
D004232:Diuretics; D009569:Nitric Oxide; D012965:Sodium Chloride; D005665:Furosemide