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.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D002867:Chromones / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects; D004049:Diethylcarbamazine / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008084:Lipoxygenase / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000201:enzymology; D010972:Platelet Activating Factor / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014661:Vasoconstriction / Q000187:drug effects
D001095:Arachidonic Acids; D002867:Chromones; D010972:Platelet Activating Factor; D016718:Arachidonic Acid; C006312:FPL 55712; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D004049:Diethylcarbamazine; D007213:Indomethacin