Renal handling of circulating nitrates in anesthetized dogs.
Nitric oxide (NO) is rapidly oxidized to nitrite (NO-2) and then to nitrate (NO-3) in biological tissues. Although urinary excretion rates of NO-3 are often used as an index of NO production in the body, very little is known regarding the kidney's ability to excrete circulating NO-3. We have evaluated the renal responses to systemic administration of sodium nitrate (NaNO3) in eight anesthetized dogs treated with the NO synthase inhibitor, nitro-L-arginine (NLA; 50 microg . kg-1 . min-1), intrarenally to minimize renal production of NO. Urinary and plasma concentrations of NO-3/NO-2 (NOX) were determined by the Greiss reaction after enzymatic reduction of NO-3 to NO-2. NLA treatment alone resulted in reductions in urinary NOX excretion rates (UNOXV, 1.13 +/- 0.2 to 0.53 +/- 0.1 nmol . min-1 . g-1) and an increase in fractional reabsorption of NOX (FRNOX, 93.8 +/- 0.6 to 97 +/- 0.6%) without changes in arterial plasma concentrations (ANOX, 18.7 +/- 1.4 to 21.2 +/- 3.7 microM). Administration of NaNO3 (10, 20, 30, and 40 microg . kg-1 . min-1) resulted in dose-dependent increases in ANOX (34.5 +/- 8.0, 46.4 +/- 7.3, 60.7 +/- 6.3, and 78.1 +/- 6.3 microM), UNOXV (1.8 +/- 0.7, 4.2 +/- 1.8, 7.0 +/- 2.0, and 11.4 +/- 3.3 nmol . min-1 . g-1), and decreases in FRNOX (93.8 +/- 2.3, 90.3 +/- 3.5, 88.6 +/- 3.2, and 84.6 +/- 3.5%). Absolute net tubular reabsorption of NO-3 showed a linear relationship with filtered loads, with no evidence of a transport maximum. These data show that, in the absence of additions from intrarenal sources, urinary excretion rates of nitrate increases progressively in response to increases in its circulating levels without exhibiting a transport maximum but with progressive decreases in fractional reabsorption.
Department of Physiology, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
M
M
Godfrey
D S
DS
Majid
D000042:Absorption; D000768:Anesthesia, General; D000818:Animals; D004285:Dogs; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D009566:Nitrates / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine*; D009573:Nitrites / Q000097:blood / Q000652:urine*; D019335:Nitroarginine / Q000494:pharmacology*; D010424:Pentobarbital; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects; D012982:Sodium, Dietary
D009566:Nitrates; D009573:Nitrites; D012982:Sodium, Dietary; D019335:Nitroarginine; C031618:sodium nitrate; D010424:Pentobarbital