Effects of exogenous prostaglandins on the release of leukotriene C4-like immunoreactivity and on coronary flow in indomethacin-treated anaphylactic guinea-pig hearts

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Abstract
Summary It is known that both vasoconstrictor cyclooxygenase products and sulfidopeptide-containing leukotrienes (LT) contribute to the biphasic coronary constriction observed in isolated perfused anaphylactic guineapig 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-PGF1α 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 PGF2α, 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 contriction. 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. Antigen-induced arrhythmias were completely suppressed by PGF2α, while PGE2 and PGI2 tended to decrease the incidence of arrhythmias and the other PG had no consistent effect. It is concluded that the pharmacological effects of the PG used on coronary flow and arrhythmias during cardiac anaphylaxis are not mediated by inhibition of release of LTC4-like immunoreactivity.