NO generation and action during changes in salt intake: roles of nNOS and macula densa.
Micropuncture studies of single nephrons have shown that macula densa solute reabsorption via a furosemide-sensitive pathway activates nitric oxide (NO) generation via neuronal NO synthase (nNOS). This pathway is enhanced during salt loading. We investigated the hypothesis that changes in NO generation via nNOS in the macula densa contribute to changes in whole kidney NO generation and action during alterations in salt intake. Groups of rats (n = 6-10) were equilibrated to high-salt (HS) or low-salt (LS) diets and were administered a vehicle (Veh), 7-nitroindazole (7-NI; a relatively selective inhibitor of nNOS), or furosemide (F; an inhibitor of macula densa solute reabsorption) with volume replacement. Compared with LS, excretion of the NO metabolites, NO2 plus NO3 (NOX) was increased during HS (LS: 9.0 +/- 0.5 vs. HS: 15.7 +/- 0.8 micromol/24 h; P < 0.001), but this difference was prevented by 7-NI (LS: 7.4 +/- 1.3 vs. HS: 9.4 +/- 1.6 micromol/24 h; NS). During nonselective blockade of NOS with NG-nitro-L-arginine methyl ester (L-NAME), renal vascular resistance (RVR) increased more in HS than LS (HS: +160 +/- 17 vs. LS: +83 +/- 10%; P < 0.001). This difference in response to nonselective NOS inhibition was prevented by pretreatment with 7-NI (HS: +28 +/- 6 vs. LS: +34 +/- 8%; NS) or F with volume replacement (HS: +79 +/- 11 vs. LS: +62 +/- 4%; NS). In conclusion, compared with salt restriction, HS intake increases NO generation and renal action that depend on nNOS and macula densa solute reabsorption.
Wilcox
C S
CS
Division of Nephrology and Hypertension, Georgetown University Medical Center, Washington, District of Columbia 20007, USA.
Deng
X
X
Welch
W J
WJ
D000042:Absorption / Q000187:drug effects; D000818:Animals; D004039:Diet, Sodium-Restricted; D004232:Diuretics / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005665:Furosemide / Q000494:pharmacology; D007191:Indazoles / Q000494:pharmacology; D007686:Kidney Tubules, Distal / Q000187:drug effects / Q000502:physiology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000652:urine; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000502:physiology*; D052248:Nitric Oxide Synthase Type I; D009573:Nitrites / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000502:physiology; D014655:Vascular Resistance / Q000502:physiology
D004232:Diuretics; D004791:Enzyme Inhibitors; D007191:Indazoles; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D005665:Furosemide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester