Differential regulation of natriuresis by 20-hydroxyeicosatetraenoic Acid in human salt-sensitive versus salt-resistant hypertension.
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.


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 micro g/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.
Laffer
Cheryl L
CL
Department of Medicine, Lenox Hill Hospital, New York University School of Medicine, New York, USA. claffer@lenoxhill.net
Laniado-Schwartzman
Michal
M
Wang
Mong-Heng
MH
Nasjletti
Alberto
A
Elijovich
Fernando
F
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D003404:Creatinine / Q000652:urine; D004039:Diet, Sodium-Restricted; D005260:Female; D005665:Furosemide / Q000627:therapeutic use; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000652:urine*; D006973:Hypertension / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009318:Natriuresis / Q000187:drug effects*; D009765:Obesity / Q000503:physiopathology; D012964:Sodium / Q000652:urine; D017673:Sodium Chloride, Dietary / Q000009:adverse effects
D006893:Hydroxyeicosatetraenoic Acids; D017673:Sodium Chloride, Dietary; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D005665:Furosemide; D012964:Sodium; D003404:Creatinine