Synthetic
leukotrienes C4 and D4 (LTC and LTD) were found to possess potent coronary
vasoconstrictor and
cardiac depressant actions on isolated guinea-pig hearts. We therefore went further to investigate the possibility that endogenously released
slow-reacting substance of anaphylaxis (
SRS-A) might be responsible for the coronary vasoconstriction and negative inotropism in guinea-pig cardiac
anaphylaxis. Results using time-course analysis as well as the specific SRS antagonist
FPL 55712 have shown that
SRS-A released during cardiac
anaphylaxis was unlikely to be responsible for the early and most dramatic phase of coronary vasoconstriction that usually occurred at the 2nd min after
antigen challenge, but could possibly be responsible for the latter and more prolonged phase occurring between the 6th and 14th min. This is because
SRS-A release was found to peak at the 4th min after
antigen challenge, 2 min after vasoconstriction had already peaked. Moreover, this early component of coronary vasoconstriction could not be blocked by
FPL 55712, whereas the latter component was significantly reduced by the antagonist. The negative inotropism following cardiac
anaphylaxis was also found to be significantly reduced by
FPL 55712, thus suggesting
SRS-A involvement. However, our experiments did not show whether the two actions were direct effects of
SRS-A or whether contractility failure was a consequence of coronary vasoconstriction.