Urinary Excretion of 20-Hete, Natriuresis and Salt-Sensitivity of Blood Pressure in Essential Hypertension
20-hydroxyeicosatetraenoic acid (20-HETE) inhibits NaCl transport in the loop of Henle. A deficit in its synthesis or action has been implicated in experimental salt-sensitive hypertension. We examined the relationship between urinary excretion of Na (UNaV) and 20-HETE in 26 essential hypertensive patients classified as salt-sensitive (SS=13) or resistant (SR=13) by an in-patient protocol of 24 hr salt-loading (HI: 160 mEq Na diet+2L saline iv) followed by 24-hr sodium deprivation (LO: 10 mEq Na diet+furosemide 120 mg in first 12 hrs). SS was defined as a fall in ambulatory systolic BP (SBP, noon to 10 pm)≥10 mmHg from HI to LO. The Table shows data in HI and in the second 12 hr period of LO, i.e., after Na depletion was achieved by furosemide. SS and SR did not differ in any of these data. 20-HETE did not correlate with race, age, or GFR. During HI, it showed a negative correlation with BMI (r=-0.44, p<0.03) and a positive one with BP (r=+0.42, p<0.04). Also, 20-HETE correlated with UNaV in all patients (r=+0.45, p<0.02), but this was due to a strong correlation in SR (r=+0.62, p<0.03), absent in SS. In LO, no correlations were observed between any of these measurements. Our data demonstrate that 20-HETE excretion varies with the state of salt-balance in human hypertension and diminishes with increasing obesity. Although excretion of 20-HETE is not different between SS and SR, there is a major difference in the relationship between excretion of this eicosanoid and natriuresis between these groups. Our data suggest that salt-sensitivity of blood pressure in human essential hypertension may result from impairment in a natriuretic mechanism dependent on 20-HETE.