Faculty Collaboration Database

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

11/07/2015

Pubmed ID

26541094

Pubmed Central ID

PMC4707990

DOI

10.1111/micc.12255

Scopus ID

2-s2.0-84953860915 (requires institutional sign-in at Scopus site)   55 Citations

Abstract

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 DD

MESH terms used to index this publication - Major topics in bold

Animals
Calcium Signaling
Coronary Vessels
Eicosanoids
Endothelium, Vascular
Gap Junctions
Humans
Hydrogen Peroxide
Muscle, Smooth, Vascular
Myocardium
Vasodilation