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Endothelium-Derived Hyperpolarization and Coronary Vasodilation: Diverse and Integrated Roles of Epoxyeicosatrienoic Acids, Hydrogen Peroxide, and Gap Junctions
Journal article   Open access   Peer reviewed

Endothelium-Derived Hyperpolarization and Coronary Vasodilation: Diverse and Integrated Roles of Epoxyeicosatrienoic Acids, Hydrogen Peroxide, and Gap Junctions

David C Ellinsworth, Shaun L Sandow, Nilima Shukla, Yanping Liu, Jamie Y Jeremy and David D Gutterman
Microcirculation, Vol.23(1), pp.15-32
2016
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PDF - Author's Accepted Version1.19 MBDownloadView
Accepted VersionPDF - Author Accepted Version Open Access
url
https://doi.org/10.1111/micc.12255View
Published Version

Abstract

human coronary microcirculation coronary blood flow endothelium-derived hyperpolarization endothelium-derived hyperpolarizing factor Ca2+-activated K+ channels epoxyeicosatrienoic acids hydrogen peroxide gap junctions myoendothelial signaling microdomains transient receptor potential channels connexins cytochrome P450 epoxygenases NADPH oxidase mitochondrial electron transport chain nitric oxide coronary artery disease
Myocardial perfusion and coronary vascular resistance are regulated by signaling metabolites released from the local myocardium that act either directly on the VSMC or indirectly via stimulation of the endothelium. A prominent mechanism of vasodilation is EDH of the arteriolar smooth muscle, with EETs and H2O2 playing important roles in EDH in the coronary microcirculation. In some cases, EETs and H2O2 are released as transferable hyperpolarizing factors (EDHFs) that act directly on the VSMCs. By contrast, EETs and H2O2 can also promote endothelial KCa activity secondary to the amplification of extracellular Ca2+ influx and Ca2+ mobilization from intracellular stores, respectively. The resulting endothelial hyperpolarization may subsequently conduct to the media via myoendothelial gap junctions or potentially lead to the release of a chemically distinct factor(s). Furthermore, in human isolated coronary arterioles dilator signaling involving EETs and H2O2 may be integrated, being either complimentary or inhibitory depending on the stimulus. With an emphasis on the human coronary microcirculation, this review addresses the diverse and integrated mechanisms by which EETs and H2O2 regulate vessel tone and also examines the hypothesis that myoendothelial microdomain signaling facilitates EDH activity in the human heart.

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Hematology
Peripheral Vascular Disease

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