Adaptation to increased dietary salt intake in the rat. Role of endogenous nitric oxide.
Previous studies have suggested that nitric oxide (NO) plays a role in regulation of renal vascular tone and sodium handling. We questioned whether the effects of NO synthase inhibition on renal function are direct or due to increased renal perfusion pressure (RPP) and whether stimulation of endogenous NO activity plays a role in adaptation to increased dietary salt intake. Intrarenal arterial infusion of the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) in control rats resulted in decreased glomerular filtration rate, renal vasoconstriction, natriuresis, and proteinuria. When RPP was held at basal levels with suprarenal aortic snare, L-NMMA had similar hemodynamic effects but decreased sodium excretion and did not induce proteinuria. Exposure of rats to high salt intake (1% NaCl drinking water) for 2 wk induced increased serum concentration and urinary excretion of the NO decomposition products, NO2 + NO3. Urinary NO2 + NO3 and sodium excretion were significantly correlated. Compared with controls, chronically salt-loaded rats also demonstrated enhanced renal hemodynamic responses to NO synthase inhibition. We conclude that the endogenous NO system directly modulates renal hemodynamics and sodium handling and participates in the renal adaptation to increased dietary salt intake. Enhanced NO synthesis in response to increased salt intake may facilitate sodium excretion and allow maintenance of normal blood pressure.
Shultz
P J
PJ
Department of Medicine, Veterans Affairs Medical Center, Minneapolis, Minnesota 55417.
Tolins
J P
JP
D000222:Adaptation, Physiological; D000594:Amino Acid Oxidoreductases / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D005919:Glomerular Filtration Rate / Q000187:drug effects; D008297:Male; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase; D009573:Nitrites / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D012982:Sodium, Dietary / Q000008:administration & dosage*; D019323:omega-N-Methylarginine
D009566:Nitrates; D009573:Nitrites; D012982:Sodium, Dietary; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases