Effect of inhibition of synthesis and receptor antagonism of SRS-A in cardiac anaphylaxis.

Abstract

The effects of infusions of the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA, 1.1 X 10(-7) mol min-1) and the antagonist of slow-reacting substance of anaphylaxis (SRS-A) FPL 55712 (1.2 X 10(-7) mol min-1) on the coronary constriction and the release of SRS-A, leukotreine C4-like immunoreactivity, thromboxane B2 and 6-keto-prostaglandin F1 alpha from perfused anaphylactic guinea-pig hearts were investigated. Both NDGA and FPL 55712 in the concentrations used induced an increase in basal coronary flow, but did not prevent the coronary flow reduction in the early phase (0-4 min) after antigen injection. On the other hand, NDGA and FPL 55712 inhibited the less pronounced long-lasting coronary flow reduction in the later phase of cardiac anaphylaxis. NDGA decreased the release of SRS-A from the anaphylactic guinea-pig hearts below or close to the detection limit of the bioassay and simultaneously diminished the release of leukotriene C4-like immunoreactivity. On the other hand, FPL 55712 did not influence the amounts of leukotriene C4-like immunoreactivity released in cardiac anaphylaxis. Neither NDGA nor FPL 55712 affected the release of immunoreactive thromboxane B2 (TXB2) from anaphylactic guinea-pig hearts. Release of 6-keto-prostaglandin F1 alpha after challenge, however, was decreased by NDGA, while FPL 55712 had no significant effect. These results suggest, that SRS-A may be a relatively more important mediator in the late phase of coronary constriction occurring during cardiac anaphylaxis, while the effects of other mediators, particularly vasoconstrictor cyclo-oxygenase products, seem to prevail in the early phase.