Renal handling of circulating nitrates in anesthetized dogs

Abstract

Nitric oxide (NO) is rapidly oxidized to nitrite ([Formula: see text]) and then to nitrate ([Formula: see text]) in biological tissues. Although urinary excretion rates of[Formula: see text] are often used as an index of NO production in the body, very little is known regarding the kidney’s ability to excrete circulating [Formula: see text]. 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 μg ⋅ kg−1 ⋅ min−1), intrarenally to minimize renal production of NO. Urinary and plasma concentrations of[Formula: see text]/[Formula: see text](NOX) were determined by the Greiss reaction after enzymatic reduction of [Formula: see text] to[Formula: see text]. 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 μM). Administration of NaNO3(10, 20, 30, and 40 μg ⋅ 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 μM), 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 [Formula: see text] 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.