Platelet-activating factor-induced vasoconstriction in rat isolated, perfused hearts: contribution of cyclo-oxygenase and lipoxygenase arachidonic acid metabolites.

The mechanism of the coronary vasoconstrictor action of platelet-activating factor (PAF) has been investigated in rat isolated, perfused hearts. PAF elicited an increase in coronary perfusion pressure which was attenuated by indomethacin- or diethylcarbamazine- pretreatment, whereas FPL55712 had a marked inhibitory effect. Accompanying the coronary vasoconstrictor response to PAF was an increase in the release of PGE2, PGF2 alpha, 6-keto-PGF1 alpha and TxB2 and the appearance of biologically-active concentrations of LTB4 and LTC4 in the cardiac effluent. Indomethacin-pretreatment prevented the increase in release of the measured cyclo-oxygenase metabolites without significantly altering the generation of either LTB4 or LTC4. Diethylcarbamazine markedly inhibited the PAF-induced release of both cyclo-oxygenase and lipoxygenase products. These findings suggest a causal role for vasoconstrictor arachidonic acid metabolites in the acute cardiac effects of PAF with the quantitatively most important contribution to the vasoconstriction made by LTC4.