Interactions between thromboxane A₂, thromboxane/prostaglandin (TP) receptors, and endothelium-derived hyperpolarization.
Endothelium-dependent smooth muscle hyperpolarization (EDH) increasingly predominates over endothelium-derived nitric oxide (NO) as a participant in vasodilation as vessel size decreases. Its underlying nature is highly variable between vessel types, species, disease states, and exact experimental conditions, and is variably mediated by one or more transferable endothelium-derived hyperpolarizing factors and/or the electrotonic spread of endothelial hyperpolarization into the media via gap junctions. Although generally regarded (and studied) as a mechanism that is independent of NO and prostanoids, evidence has emerged that the endothelium-derived contracting factor and prostanoid thromboxane A2 can modulate several signalling components central to EDH, and therefore potentially curtail vasodilation through mechanisms that are distinct from those putatively involved in direct smooth muscle contraction. Notably, vascular production of thromboxane A2 is elevated in a number of cardiovascular disease states that promote endothelial dysfunction. This review will therefore discuss the mechanisms through which thromboxane A2 interacts with and modulates EDH, and will also consider the implications of such cross-talk in vasodilator control in health and disease.
Bristol Heart Institute, University of Bristol, Queens Building Level 7, Upper Maudlin St, Bristol Royal Infirmary, Upper Maudlin Street, Bristol BS2 8HW, UK.
David C
DC
Ellinsworth
Nilima
N
Shukla
Ingrid
I
Fleming
Jamie Y
JY
Jeremy
D000818:Animals; D001685:Biological Factors / Q000378:metabolism*; D017629:Gap Junctions / Q000502:physiology; D006801:Humans; D011453:Prostaglandins / Q000378:metabolism*; D011982:Receptors, Prostaglandin / Q000378:metabolism*; D017482:Receptors, Thromboxane / Q000378:metabolism*; D013928:Thromboxane A2 / Q000378:metabolism*
D001685:Biological Factors; D011453:Prostaglandins; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; C067410:endothelium-dependent hyperpolarization factor; D013928:Thromboxane A2
Calcium-activated K+ channels; Endothelium-dependent hyperpolarization; Gap junctional communication; TP receptors; Thromboxane A2