Urinary 20-hydroxyeicosatetraenoic acid is associated with endothelial dysfunction in humans

Natalie C. Ward, Jennifer Rivera, Jonathan Hodgson, Ian B. Puddey, Lawrie J. Beilin, J R Falck, Kevin D. Croft

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Abstract

Background - 20-Hydroxyeicosatetraenoic acid (20-HETE) is a cytochrome P450 (ω-hydroxylase) metabolite of arachidonic acid with vasoconstrictor activity that may be involved in the pathogenesis of hypertension. In humans, there are few data relating 20-HETE to vascular pathophysiology. This study aimed to determine whether urinary 20-HETE excretion is related to blood pressure or vascular endothelial function in humans. Methods and Results - Sixty-six subjects (37 males, 29 females), including 29 with untreated hypertension, had urinary 20-HETE excretion measured by gas chromatography/mass spectrometry. There was no significant difference for 20-HETE excretion between hypertensive and normotensive subjects. 20-HETE excretion was positively related to body mass index and sodium excretion. There was a significant inverse association between urinary 20-HETE and endothelium-dependent vasodilation measured by flow-mediated dilation of the brachial artery (P=0.006). There was no association with vasodilator responses to nitroglycerin. In multiple regression analysis, 20-HETE remained an independent predictor of endothelium-dependent vasodilation after adjustment for age, body mass index, and blood pressure. When gender was included in the model, the relationship between 20-HETE and flow-mediated dilation was attenuated. Separate analysis by gender revealed that in women, hypertensive subjects had significantly higher 20-HETE excretion than normotensive subjects, but this was not seen in men. In women, 20-HETE was positively related to diastolic and systolic blood pressure. In men, 20-HETE was positively related to body mass index. Conclusions - This is the first demonstration of an association between 20-HETE excretion and in vivo vascular function in humans. Given the negative modulatory role of nitric oxide on ω-hydroxylase, the present results suggest a potentially important role for 20-HETE in human vascular physiology.

Original languageEnglish (US)
Pages (from-to)438-443
Number of pages6
JournalCirculation
Volume110
Issue number4
DOIs
StatePublished - Jul 27 2004

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Keywords

  • Blood pressure
  • Endothelium
  • Fatty acids
  • Hypertension

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Ward, N. C., Rivera, J., Hodgson, J., Puddey, I. B., Beilin, L. J., Falck, J. R., & Croft, K. D. (2004). Urinary 20-hydroxyeicosatetraenoic acid is associated with endothelial dysfunction in humans. Circulation, 110(4), 438-443. https://doi.org/10.1161/01.CIR.0000136808.72912.D9