Physiological concentrations of epinephrine potentiate thromboxane A2 release from platelets in the isolated rat heart.
The isolated rat heart perfused with washed platelets was used as a model to examine platelet-vessel wall interactions. Release of prostacyclin and thromboxane A2 was measured, using a cascade of smooth muscle bioassay tissues or radioimmunoassays of the stable hydration products. In hearts perfused with rabbit or human platelets, injection of sodium arachidonate caused release of both prostacyclin and thromboxane A2. In hearts perfused with aspirin-pretreated platelets, arachidonate released only prostacyclin indicating that thromboxane A2 originates largely in the platelets. Infusion of epinephrine (0.6-6 nmol/liter) through the heart potentiated arachidonate-induced release of thromboxane A2. Similar potentiation of thromboxane A2 release was observed in rat hearts perfused with either rabbit or human platelets, and in rabbit hearts perfused with rabbit platelets. In contrast, when rabbit platelets were infused through an incubation coil of tubing in place of the heart, epinephrine did not alter thromboxane A2 release. There was no significant loss of rabbit platelets on perfusion through rat hearts, and no aggregates were observed in the effluent either before or immediately after arachidonate injections, even in the presence of epinephrine. Thus, potentiation of thromboxane A2 production could not be explained by aggregation. However, it is clear from these studies that physiological concentrations of epinephrine can potentiate thromboxane A2 release from platelets when they are stimulated by arachidonic acid within the heart. This could result from a redirection of arachidonate metabolism to a local potentiating factor in the vessel wall. Potentiation of thromboxane A2 release might contribute to myocardial ischemia associated with platelet activation.
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D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001681:Biological Assay; D001792:Blood Platelets / Q000378:metabolism*; D002417:Cattle; D004357:Drug Synergism; D004837:Epinephrine / Q000494:pharmacology*; D011464:Epoprostenol / Q000378:metabolism; D005260:Female; D006801:Humans; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D009206:Myocardium / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013552:Swine; D013928:Thromboxane A2 / Q000378:metabolism* / Q000494:pharmacology; D013929:Thromboxane B2 / Q000378:metabolism
D001095:Arachidonic Acids; D016718:Arachidonic Acid; D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D004837:Epinephrine