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. 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 omega-hydroxylase, the present results suggest a potentially important role for 20-HETE in human vascular physiology.
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. 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 omega-hydroxylase, the present results suggest a potentially important role for 20-HETE in human vascular physiology.
Authors: Jennifer Cheng; Victor Garcia; Yan Ding; Cheng-Chia Wu; Krutanjali Thakar; John R Falck; Errabelli Ramu; Michal Laniado Schwartzman Journal: Arterioscler Thromb Vasc Biol Date: 2012-06-21 Impact factor: 8.311
Authors: Albert W Dreisbach; Stanley V Smith; Patrick B Kyle; Manjunath Ramaiah; Margaret Amenuke; Michael R Garrett; Seth T Lirette; Michael E Griswold; Richard J Roman Journal: Prostaglandins Other Lipid Mediat Date: 2014-08-22 Impact factor: 3.072
Authors: Ana C Dordea; Sara Vandenwijngaert; Victor Garcia; Robert E T Tainsh; Daniel I Nathan; Kaitlin Allen; Michael J Raher; Laurel T Tainsh; Fan Zhang; Wolfgang S Lieb; Sarah Mikelman; Andrew Kirby; Christine Stevens; Robrecht Thoonen; Allyson G Hindle; Patrick Y Sips; John R Falck; Mark J Daly; Peter Brouckaert; Kenneth D Bloch; Donald B Bloch; Rajeev Malhotra; Michal L Schwartzman; Emmanuel S Buys Journal: Am J Physiol Heart Circ Physiol Date: 2016-05-03 Impact factor: 4.733