Urinary 20-hydroxyeicosatetraenoic acid is associated with endothelial dysfunction in humans.
BACKGROUND
20-hydroxyeicosatetraenoic acid (20-HETE) is a cytochrome P450 (omega-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.


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 omega-hydroxylase, the present results suggest a potentially important role for 20-HETE in human vascular physiology.
Ward
Natalie C
NC
School of Medicine & Pharmacology, University of Western Australia & West Australian Institute of Medical Research, Perth, Australia.
Rivera
Jennifer
J
Hodgson
Jonathan
J
Puddey
Ian B
IB
Beilin
Lawrie J
LJ
Falck
John R
JR
Croft
Kevin D
KD
D015992:Body Mass Index; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000503:physiopathology*; D005260:Female; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000652:urine*; D006973:Hypertension / Q000652:urine*; D008297:Male; D008955:Models, Cardiovascular; D014463:Ultrasonography; D014664:Vasodilation
D006893:Hydroxyeicosatetraenoic Acids; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid