Published Online
on July 19, 2004

A more recent version of this article appeared on July 27, 2004

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Submitted on December 2, 2003
Revised on March 9, 2004
Accepted on March 30, 2004

Urinary 20-Hydroxyeicosatetraenoic Acid Is Associated With Endothelial Dysfunction in Humans

Natalie C. Ward PhD, Jennifer Rivera BSc(Hon), Jonathan Hodgson PhD, Ian B. Puddey MD, Lawrie J. Beilin MD, John R. Falck PhD, and Kevin D. Croft PhD^*

From the School of Medicine and Pharmacology (N.C.W., J.R., J.H., I.B.P., L.J.B., K.D.C.), University of Western Australia & West Australian Institute of Medical Research, Perth, Australia, and Biochemistry Department (J.R.F.), University of Texas Southwestern Medical Center, Dallas, Tex.

^* To whom correspondence should be addressed. E-mail: kcroft{at}cyllene.uwa.edu.au.

Background--20-Hydroxyeicosatetraenoic acid (20-HETE) is a cytochrome P450 (-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 -hydroxylase, the present results suggest a potentially important role for 20-HETE in human vascular physiology.

Key words: fatty acids • blood pressure • hypertension • endothelium

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