Endothelium-Derived Hyperpolarization and Coronary Vasodilation: Diverse and Integrated Roles of Epoxyeicosatrienoic Acids, Hydrogen Peroxide, and Gap Junctions. Microcirculation 2016 Jan;23(1):15-32
Date
11/07/2015Pubmed ID
26541094Pubmed Central ID
PMC4707990DOI
10.1111/micc.12255Scopus ID
2-s2.0-84953860915 (requires institutional sign-in at Scopus site) 55 CitationsAbstract
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 H(2)O(2) playing important roles in EDH in the coronary microcirculation. In some cases, EETs and H(2)O(2) are released as transferable hyperpolarizing factors (EDHFs) that act directly on the VSMCs. By contrast, EETs and H(2)O(2) can also promote endothelial KCa activity secondary to the amplification of extracellular Ca(2+) influx and Ca(2+) 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 H(2)O(2) 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 H(2)O(2) regulate vessel tone and also examines the hypothesis that myoendothelial microdomain signaling facilitates EDH activity in the human heart.
Author List
Ellinsworth DC, Sandow SL, Shukla N, Liu Y, Jeremy JY, Gutterman DDMESH terms used to index this publication - Major topics in bold
AnimalsCalcium Signaling
Coronary Vessels
Eicosanoids
Endothelium, Vascular
Gap Junctions
Humans
Hydrogen Peroxide
Muscle, Smooth, Vascular
Myocardium
Vasodilation