Submitted to: Hypertension
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/21/2007
Publication Date: 3/13/2008
Citation: Driesbach, A.W., Rice, J.C., Japa, S., Newman, J.W., Sigel, A., Gill, R., Hess, A.E., Cemo, A.C., Fonseca, J.P., Hammock, B.D., Lertora, J., Hamm, J.P. Salt loading increases urinary excretion of linoleic acid diols and triols in healthy human subjects. 2008 Hypertension. 51:755-761.
Interpretive Summary: Physiologically, the kidney is critical for the regulation of sodium excretion, which can have dramatic impacts on blood pressure in some individuals. While receiving a significant amount of attention, there is much remaining to understand regarding the metabolic regulation of sodium maintenance. In particular, dietary linoleic acid levels have been reported to affect sodium retention. In this study, the excretion of urinary linoleate metabolites was quantified in a salt loading/depletion regimen in healthy men. The urinary excretion of linoleate diols and triols increased significantly during intravenous salt loading, when compared to the salt depleted state. These results are consistent with other reports of fatty acid metabolism-dependent modulation of sodium channels, and may indicate that the salt-stimulated production of linoleic acid diols and triols may inhibit tubular sodium reabsorption, thereby assisting the excretion of the sodium load.
Technical Abstract: Urinary linoleate (LA) metabolite excretion was investigated in subjects exposed to a salt loading/salt depletion regimen. Twelve healthy subjects were recruited from the New Orleans population (pre-Katrina) and admitted to Tulane-LSU Charity Hospital GCRC after a 5-day outpatient lead in phase on a 160 mmole sodium (Na) diet. On inpatient Day 1 the subjects were maintained on the 160 mmole Na diet and a 24hr urine was collected. On Day 2 the subjects received 2 L of Normal Saline IV over 4hr and continued on 160 Na+ mmole diet (total 460 mmole Na). Two 12hr urine collections were obtained. On Day 3 the patient received three 40 mg oral doses of furosemide and two 12hr urine collections were obtained and the patient was given a 10 mmole Na+ diet. The urinary LA diols (9,10-DiHOME and 12,13-DiHOME) and triols (9,10,13-TriHOME and 9,12,13-TriHOME) were measured by HPLC-tandem quadrupole mass spectroscopy. Repeated measures were evaluated by ANOVA with a Tukey Test to compare linoleic acid metabolite levels during salt-loaded and salt-depleted periods. The urinary excretion of LA diols and triols increased significantly during intravenous salt loading as compared to the salt-depleted periods and Day 1. The salt-stimulated production of linoleic acid diols and triols may inhibit tubular sodium reabsorption, thereby assisting the excretion of the sodium load.