Relation Between Pressure Natriuresis and Urinary Excretion of Nitrate/Nitrite in Anesthetized Dogs

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Abstract
Abstract Alterations in intrarenal nitric oxide (NO) formation during changes in renal arterial pressure (RAP) have been suggested as a mechanism mediating pressure natriuresis. To test this hypothesis further, we examined the relation between RAP and the urinary excretion rate of nitrate/nitrite (NO 3 − /NO 2 − ; NO metabolites) in anesthetized sodium-replete dogs before (n=9) and during (n=6) intrarenal infusion of the NO synthesis inhibitor nitro- l -arginine (NLA; 50 μg · kg −1 · min −1 ). Urinary NO 3 − /NO 2 − concentrations were measured with the Griess reaction and spectrophotometry methods after enzymatic reduction of NO 3 − to NO 2 − in the samples. During control conditions, there were decreases in the urinary NO 3 − /NO 2 − excretion rate in response to reductions in RAP (150 to 75 mm Hg; slope, 0.04±0.01 nmol · min −1 · g −1 · mm Hg −1 ) in association with decreases in urinary sodium excretion (U Na V). There was a positive correlation between changes in NO 3 − /NO 2 − excretion rate and changes in RAP ( r =.48; P <.005) or U Na V ( r =.59; P <.001). NLA infusion resulted in decreases in NO 3 − /NO 2 − excretion rate (4.8±1.4 to 1.0±0.3 nmol · min −1 · g −1 ) in association with reductions in U Na V (4.3±0.3 to 0.7±0.2 μL · min −1 · g −1 ), fractional excretion of sodium (2.9±0.2% to 0.5±0.1%), and renal blood flow (4.8±0.3 to 3.3±0.2 mL · min −1 · g −1 ), without changes in glomerular filtration rate. Furthermore, there was a marked attenuation of the NO 3 − /NO 2 − and sodium excretory responses to alterations in RAP during NO synthesis inhibition. In another four dogs, it was observed that urinary NO 3 − /NO 2 − excretion rate did not change during administration of thiazide and amiloride diuretics, indicating that the NO 3 − /NO 2 − excretory responses to alterations in RAP were not simply due to changes in urine flow rate or sodium excretion. These findings are consistent with the hypothesis that during acute changes in RAP, intrarenal changes in NO production rate may be responsible for the changes in sodium excretion.