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(Hypertension. 1995;25:860-865.)
© 1995 American Heart Association, Inc.

Articles

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

Dewan S. A. Majid; Murrell Godfrey; Matthew B. Grisham; L. Gabriel Navar

From the Department of Physiology, Tulane University School of Medicine, New Orleans, and the Department of Physiology and Biophysics, Louisiana State University Medical Center, Shreveport (M.B.G.), La.

Correspondence to Dewan S.A. Majid, PhD, Department of Physiology SL39, Tulane University School of Medicine, 1430 Tulane Ave, New Orleans, LA 70112.

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 (NO₃^-/NO₂^-; 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 NO₃^-/NO₂^- concentrations were measured with the Griess reaction and spectrophotometry methods after enzymatic reduction of NO₃^- to NO₂^- in the samples. During control conditions, there were decreases in the urinary NO₃^-/NO₂^- 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_NaV). There was a positive correlation between changes in NO₃^-/NO₂^- excretion rate and changes in RAP (r=.48; P<.005) or U_NaV (r=.59; P<.001). NLA infusion resulted in decreases in NO₃^-/NO₂^- excretion rate (4.8±1.4 to 1.0±0.3 nmol · min^-1 · g^-1) in association with reductions in U_NaV (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 NO₃^-/NO₂^- and sodium excretory responses to alterations in RAP during NO synthesis inhibition. In another four dogs, it was observed that urinary NO₃^-/NO₂^- excretion rate did not change during administration of thiazide and amiloride diuretics, indicating that the NO₃^-/NO₂^- 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.

Key Words: nitric oxide • arginine • renal circulation • natriuresis

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