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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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. CONCLUSION: 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.[1]


  1. Short-term modulation of distal tubule fluid nitric oxide in vivo by loop NaCl reabsorption. Levine, D.Z., Burns, K.D., Jaffey, J., Iacovitti, M. Kidney Int. (2004) [Pubmed]
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