Published online before print January 6, 2003, doi: 10.1161/01.CIR.0000046269.52392.14
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(Circulation. 2003;107:574.)
© 2003 American Heart Association, Inc.
Clinical Investigation and Reports |
Differential Regulation of Natriuresis by 20-Hydroxyeicosatetraenoic Acid in Human Salt-Sensitive Versus Salt-Resistant Hypertension
From the Department of Medicine, Lenox Hill Hospital, New York University School of Medicine, New York (C.L.L., F.E.); and the Department of Pharmacology, New York Medical College, Valhalla (M.L.-S., M.-H.W., A.N.).
Correspondence to Dr Cheryl Laffer, Lenox Hill Hypertension and Cardiovascular Center, 210 East 64th St, New York, NY 10021. E-mail claffer{at}lenoxhill.net
Background— Twenty-hydroxyeicosatetraenoic acid (20-HETE) is a cytochrome P450 metabolite of arachidonic acid that produces vasoconstriction and inhibition of renal tubular sodium transport. In Dahl rats, a 20-HETE deficiency plays a role in salt-sensitive (SS) hypertension. In humans, there are no data on regulation of 20-HETE by salt intake or on a role for this compound in SS hypertension.
Methods and Results— Thirteen salt-resistant (SR) and 13 SS hypertensive subjects had urine 20-HETE excretion measured during salt-loading and depletion. In all patients, 20-HETE was 66.6% higher in the salt-replete (1.75±0.25 µg/h) than in the salt-depleted state (1.05±0.16, P<0.003). There was no difference in 20-HETE excretion between SR and SS patients in either state of salt balance. In SR patients, sodium excretion during salt-loading correlated with 20-HETE (r=0.61, P<0.03) but not with blood pressure. In contrast, in SS patients, sodium excretion did not correlate with 20-HETE but did correlate with blood pressure (r=0.66, P<0.02). Finally, in the SS group only, there was a negative correlation between body mass index and 20-HETE excretion (r=-0.79, P<0.002) that was present during both salt-loading and depletion.
Conclusions— We demonstrate for the first time that 20-HETE excretion is regulated by salt intake in hypertension. We find a disrupted relationship between sodium excretion and 20-HETE in SS patients, which results in dependence of their salt excretion on blood pressure and may be related to the magnitude of their obesity. We conclude that salt-sensitivity of blood pressure in essential hypertension may result from impairment of a natriuretic mechanism dependent on 20-HETE.
Key Words: blood pressure • obesity • sodium
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