z-logo
Premium
12‐ and 15‐Hydroxyeicosatetraenoic Acids (HETEs) Function as Endothelium‐Derived Hyperpolarizing Factors (EDHFs) in Human Coronary Arterioles
Author(s) -
Larsen Brandon T,
Miura Hiroto,
Campbell William B,
Gutterman David D
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.952.17
Subject(s) - iberiotoxin , apamin , charybdotoxin , hyperpolarization (physics) , chemistry , medicine , endocrinology , vasodilation , endothelium , hydroxyeicosatetraenoic acid , potassium channel , arachidonic acid , biology , biochemistry , stereochemistry , enzyme , nuclear magnetic resonance spectroscopy
12‐ and 15‐HETEs are lipoxygenase (LO)‐derived arachidonic acid metabolites that are produced abundantly by human coronary arterioles (HCAs); however, their biological role is unknown. We hypothesized that 12‐ and 15‐HETEs function as EDHFs. HCAs were isolated from atrial appendages and studied by immunohistochemistry (IHC), membrane potential (E m ) recording, and videomicroscopy. IHC revealed endothelial expression of 12‐ and 15‐LO. In endothelium‐denuded vessels, 1 μM 12‐HETE induced smooth muscle hyperpolarization (E m ‐54±2 vs ‐43±1 mV at baseline, n=4, p<0.05) that was attenuated by charybdotoxin + apamin (K + channel inhibitors that block EDHFs; ‐43±1 vs ‐37±1 with inhibitors alone, n=4, p<0.05 vs. 12‐HETE alone). 12‐ or 15‐HETE elicited concentration‐dependent vasodilation (68±5% and 67±6% at 10 μM, respectively, n=11 each) that was inhibited by 40 mM KCl (3±6% and 1±4%, respectively, n=5, p<0.05) but not by endothelial denudation (65±17% and 64±6%, respectively, n=3). 12‐ and 15‐HETE‐induced dilations were reduced by charybdotoxin + apamin (16±6% and 6±5%, respectively, n=4, p<0.05), but not by iberiotoxin (a specific inhibitor of large‐conductance Ca 2+ ‐activated K + channels; 92±8% and 87±2%, respectively, n=2). We conclude that 12‐ and 15‐HETEs elicit endothelium‐independent dilation and hyperpolarization of HCAs by a mechanism requiring K + channels. These findings support a role for LO‐derived eicosanoids as EDHFs and suggest that these HETEs modulate vasomotor tone in the human heart.

This content is not available in your region!

Continue researching here.

Having issues? You can contact us here