RENAL HANDLING OF CIRCULATING NITRATES IN ANESTHETIZED DOGS

Nitric oxide (NO) is rapidly oxidized to nitrite (NO2-) and then to ni trate (NO3-) in biological tissues. Although urinary excretion rates o f NO3- are often used as an index of NO production in the body, very l ittle is known regarding the kidney's ability to excrete circulating N O3-. 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 mu g.kg(-1).min(-1)), intrarenally to minimize renal production of NO. Urinary and plasma c oncentrations of NO3-/NO2- (NOX) were determined by the Greiss reactio n after enzymatic reduction of NO3- to NO2-. NLA treatment alone resul ted 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 reab sorption of NOX (FRNOX, 93.8 +/- 0;6 to 97 +/- 0.6%) without changes i n arterial plasma concentrations (A(NOX), 18.7 +/- 1.4 to 21.2 +/- 3.7 mu M). Administration of NaNO3 (10, 20, 30, and 40 mu g.kg(-1).min(-1 )) resulted in dose-dependent increases in A(NOX) (34.5 +/- 8.0, 46.4 +/- 7.3, 60.7 +/- 6.3, and 78.1 +/- 6.3 mu M), UNOXV (1.8 +/- 0.7, 4.2 +/- 1.8, 7.0 +/- 2.0, and 11.4 +/- 3.3 nmol.min(-1).g(-1)), and decre ases in FRNOX (93.8 +/- 2.3, 90.3 +/- 3.5, 88.6 +/- 3.2, and 84.6 +/- 3.5%). Absolute net tubular reabsorption of NO3- showed a linear relat ionship with filtered loads, with no evidence of a transport maximum. These data show that, in the absence of additions from intrarenal sour ces, urinary excretion rates of nitrate increases progressively in res ponse to increases in its circulating levels without exhibiting a tran sport maximum but with progressive decreases in fractional reabsorptio n.