Thromboxane and prostacyclin release during cardiac immediate hypersensitivity reactions in vitro.
Cardiac immediate hypersensitivity reactions in vitro are characterized by tachycardia, arrhythmias and coronary constriction. Whereas endogenous cardiac histamine release is responsible for the generation of arrhythmias, metabolites of arachidonic acid mediate the fall in coronary flow. In the present study, we have shown that antigenic challenge of sensitized guinea-pig hearts results in the release into the coronary effluent of immunoreactive thromboxane B2, 6-keto prostaglandin (PG) F1 alpha and PGF2 alpha. Thromboxane B2 was the predominant metabolite generated. After the administration of histamine (1-100 micrograms) or a partially purified preparation of slow-reacting substance of anaphylaxis (5-100 U) to the sensitized heart there was no detectable release of thromboxane B2 into the coronary effluent. After the administration of sodium arachidonate (3 X 10(-6) M) to the sensitized heart 40 min after antigenic challenge, there was a predominant release of 6-keto PGF1 alpha into the coronary effluent. Pretreatment of sensitized hearts with aspirin (5.5 X 10(-5) M), indomethacin (1.4 X 10(-5) M) or 1-(2-isopropylphenyl)imidazole (5.4 X 10(-5) M) resulted in inhibition of antigen-induced thromboxane B2 release and coronary vasoconstriction. These results suggest that during immediate hypersensitivity reactions, the coronary vasculature may be predisposed to ischemic and thrombotic episodes as a result of thromboxane release. Thromboxane formation occurs independently of the actions of histamine and slow-reacting substance of anaphylaxis and, since it is not generated preferentially by the coronary circulation of the sensitized heart in response to arachidonate infusion, it is plausible to suggest that it is of mast cell origin.
D015121:6-Ketoprostaglandin F1 alpha; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D006168:Guinea Pigs; D006969:Hypersensitivity, Immediate / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D011460:Prostaglandins F / Q000378:metabolism*; D013929:Thromboxane B2 / Q000378:metabolism*; D013931:Thromboxanes / Q000378:metabolism*
D001095:Arachidonic Acids; D011460:Prostaglandins F; D013931:Thromboxanes; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha