title: Effects of exogenous prostaglandins on the release of leukotriene C4-like immunoreactivity and on coronary flow in indomethacin-treated anaphylactic guinea-pig hearts.
abstract: It is known that both vasoconstrictor cyclooxygenase products and sulfidopeptide-containing leukotrienes (LT) contribute to the biphasic coronary constriction observed in isolated perfused anaphylactic guinea-pig hearts. We have now investigated the effects of the cyclooxygenase inhibitor indomethacin and of several exogenous prostaglandins (PG) on the release of LTC4-like immunoreactivity and on various symptoms of cardiac anaphylaxis. Indomethacin decreased basal coronary flow and delayed the onset of coronary vasoconstriction after antigenic challenge. Furthermore, indomethacin inhibited cardiac release of 6-keto-PGF1 alpha and thromboxane (TX) B2 and simultaneously enhanced the antigen-induced release of LTC4-like immunoreactivity significantly. Neither the vasodilators PGE2 and PGI2 nor the vasoconstrictors PGF2 alpha, PGD2 and 11,9-epoxymethano-PGH2, a compound with biological properties similar to TXA2, affected the anaphylactic release of immunoreactive LTC4 in the presence of indomethacin. These results suggest that the indomethacin-induced increase in LT release is not due to inhibition of synthesis of a cyclooxygenase product, which normally curbs anaphylactic release of immunoreactive LTC4. The indomethacin effect may rather be explained by diversion of arachidonic acid metabolism away from fatty acid cyclooxygenase towards the synthesis of lipoxygenase products. Although the various PG did not significantly affect cardiac release of LTC4-like immunoreactivity, they antagonized the anaphylactic coronary constriction. This antagonism may be due to direct effects of the PG on vascular smooth muscle tone as well as to indirect effects on the release of anaphylactic mediators not related to LT like histamine and platelet-activating factor.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000494:pharmacology; D000707:Anaphylaxis / Q000503:physiopathology*; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects*; D015232:Dinoprostone; D011464:Epoprostenol / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D011453:Prostaglandins / Q000494:pharmacology*; D011458:Prostaglandins E / Q000494:pharmacology; D011863:Radioimmunoassay; D013189:SRS-A / Q000378:metabolism*; D013929:Thromboxane B2 / Q000494:pharmacology
chemical_list: D011453:Prostaglandins; D011458:Prostaglandins E; D013189:SRS-A; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D015232:Dinoprostone; D007213:Indomethacin