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

Cheryl L. Laffer, Michal Laniado-Schwartzman, Mong Heng Wang, Alberto Nasjletti, Fernando Elijovich

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)574-578
Number of pages5
JournalCirculation
Volume107
Issue number4
DOIs
StatePublished - Feb 4 2003

Fingerprint

Natriuresis
Salts
Hypertension
Sodium
20-hydroxy-5,8,11,14-eicosatetraenoic acid
Blood Pressure
Inbred Dahl Rats
Hydroxyeicosatetraenoic Acids

Keywords

  • Blood pressure
  • Obesity
  • Sodium

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Differential regulation of natriuresis by 20-hydroxyeicosatetraenoic acid in human salt-sensitive versus salt-resistant hypertension. / Laffer, Cheryl L.; Laniado-Schwartzman, Michal; Wang, Mong Heng; Nasjletti, Alberto; Elijovich, Fernando.

In: Circulation, Vol. 107, No. 4, 04.02.2003, p. 574-578.

Research output: Contribution to journalArticle

Laffer, Cheryl L. ; Laniado-Schwartzman, Michal ; Wang, Mong Heng ; Nasjletti, Alberto ; Elijovich, Fernando. / Differential regulation of natriuresis by 20-hydroxyeicosatetraenoic acid in human salt-sensitive versus salt-resistant hypertension. In: Circulation. 2003 ; Vol. 107, No. 4. pp. 574-578.
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abstract = "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.",
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T1 - Differential regulation of natriuresis by 20-hydroxyeicosatetraenoic acid in human salt-sensitive versus salt-resistant hypertension

AU - Laffer, Cheryl L.

AU - Laniado-Schwartzman, Michal

AU - Wang, Mong Heng

AU - Nasjletti, Alberto

AU - Elijovich, Fernando

PY - 2003/2/4

Y1 - 2003/2/4

N2 - 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.

AB - 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.

KW - Blood pressure

KW - Obesity

KW - Sodium

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