The effect of prostaglandins and thromboxane A2 on coronary vessel tone--mechanisms of action and therapeutic implications.
Prostaglandins (PGI2, PGE2, PGF2 alpha) and thromboxane (TX) A2 are vasoactive, cell membrane-derived lipid mediators that are formed in response to stimulation of vascular smooth muscle cells by a variety of chemical agonists. Different receptor subtypes mediate the contractile and relaxing effects of prostaglandins and TXA2 on coronary vascular smooth muscle: a high-affinity (kD: > or = 1 nM) PGH2/TXA2 receptor mediates the contractile actions of TXA2; a low-affinity (kD 100-200 nM) receptor mediates the contractile actions of other prostaglandins ('primary prostaglandin receptor') and a PGI2 receptor (kD > or = 20 nM) mediates vessel relaxation. These receptors are coupled to intracellular signal transduction pathways via different G-proteins and modify muscle tone by control of cytosolic Cai++. Ca(++)- and ATP-dependent K-channels are regulated by PGI2 (opening) and TXA2 (closure) and are involved in the setting of coronary smooth muscle tone. There is experimental and clinical evidence for enhanced local TXA2 levels, an increased number of platelet TXA2 receptors and a reduced number of PGI2 receptors in acute myocardial infarction. There is also experimental evidence for increased synthesis of PGF2 alpha-receptors in vascular smooth muscle that may mediate smooth muscle proliferation. The interference of both TXA2 and PGI2 with K(+)-channels in coronary arteries may have important implications for coronary vasospasm and ischaemia-related cardiac hypoperfusion.
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Institute für Pharmakologie, Heinrich-Heine-Universität Düsseldorf, Germany.
D000818:Animals; D003327:Coronary Disease / Q000188:drug therapy / Q000503:physiopathology; D003331:Coronary Vessels / Q000502:physiology; D006801:Humans; D007473:Ion Channels / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D011453:Prostaglandins / Q000502:physiology*; D018055:Receptors, Eicosanoid / Q000502:physiology; D015398:Signal Transduction; D013928:Thromboxane A2 / Q000502:physiology*
D007473:Ion Channels; D011453:Prostaglandins; D018055:Receptors, Eicosanoid; D013928:Thromboxane A2