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(Circulation. 2004;110:438-443.)
© 2004 American Heart Association, Inc.

Original Articles

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; 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.

Correspondence to Associate Professor Kevin D Croft, School of Medicine & Pharmacology, Box X2213 GPO, Perth, West Australia 6847. E-mail kcroft{at}cyllene.uwa.edu.au

Received December 2, 2003; de novo received March 9, 2004; accepted March 30, 2004.

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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