Role of nitric oxide in tubuloglomerular feedback: effects of dietary salt.
1. The tubuloglomerular feedback (TGF) response operates primarily by vasoconstriction of the afferent arteriole and a fall in glomerular capillary pressure (PGC) and single-nephron glomerular filtration rate (SNGFR) during increased NaCl reabsorption in the macula densa (MD). Numerous studies have suggested that nitric oxide (NO) is synthesized by the MD and acts to suppress TGF. As a high-salt (HS) diet has been found to blunt TGF, we tested the effects of salt intake on NO-dependent changes in TGF. 2. In the first series of experiments, values of SNGFR were contrasted from samples of tubular fluid taken from the proximal tubule (PT; MD delivery interrupted) and the distal tubule DT; MD delivery intact). Compared with HS rats, the difference between PT and DT values of SNGFR was increased in low-salt (LS) diet rats (4.3 +/- 0.4 vs 10.3 +/- 1.2 nL/min, respectively; P < 0.001). Intravenous infusion of NG-monomethyl-L-arginine (L-NMMA), in pressor doses increased the difference between PT and DT values of SNGFR of HS rats (4.3 +/- 0.4 vs 9.5 +/- 1.2 nL/min before and during L-NMMA, respectively; P < 0.001) without significantly affecting values in LS rats (10.3 +/- 1.2 vs 12.3 +/- 1.4 nL/min before and during L-NMMA, respectively; NS). 3. A second series of experiments assessed TGF responses directly. Changes in stop-flow pressure (PSF; an index of PGC) were measured in response to graded perfusion of the loop of Henle (LH) with artificial tubular fluid. Loop perfusion with 10(-3) mol/L L-NMMA did not affect the PSF responses of LS rats but did reduce (P < 0.01) the PSF of HS rats during perfusion at 20 nL/min (-1.5 +/- 0.4 mmHg; P < 0.01), 30 nL/min (-1.8 +/- 0.5 mmHg; P < 0.01) and 40 nL/min (-2.2 +/- 0.5 mmHg; P < 0.001). 4. We conclude that the TGF response is increased by suppression of NOS activity during HS but not LS intake.
Welch
W J
WJ
Division of Nephrology and Hypertension, Georgetown University Medical Centre, Washington, DC, USA. welchw@medlib.iaims.georgetown.edu
Wilcox
C S
CS
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005246:Feedback / Q000187:drug effects*; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017673:Sodium Chloride, Dietary / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D017673:Sodium Chloride, Dietary; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester