Mechanisms of the coronary vascular effects of platelet-activating factor in the rat perfused heart.
1. In a previous study it was demonstrated that bolus injections of platelet-activating factor (PAF) in the rat perfused heart resulted in coronary vasodilatation, vasoconstriction or the combination of both, depending on the amount of PAF that was injected. In the present study, the mechanisms of these coronary vascular effects of PAF in the rat perfused heart were investigated. 2. Pretreatment of the rat perfused heart with the PAF antagonists FR-900452 or BN-52021 did not affect the vasodilator effect of PAF but eliminated the vasoconstrictor effect of PAF. FR-900452 had no effect on the vasoconstrictor response to leukotriene C4 (LTC4) or LTD4. 3. The cyclo-oxygenase inhibitor, indomethacin, did not modify the coronary vascular effects of PAF. However L-649,923 (a leukotriene antagonist) and MK-886 (a leukotriene synthesis inhibitor) eliminated both the vasodilator and vasoconstrictor effects of PAF. 4. When leukotrienes were administered by bolus injection in the rat perfused heart, LTB4 produced vasodilatation while LTC4 and LTD4 produced vasoconstriction. L-649,923 blocked both the vasodilator and vasoconstrictor effects of the leukotrienes tested. 5. The results suggest that lipoxygenase products are responsible for both the vasodilator and vasoconstrictor actions of PAF in the coronary vasculature of the rat perfused heart while the cyclo-oxygenase products do not play a significant role. The ineffectiveness of PAF antagonists in blocking the vasodilatation produced by PAF is compatible with the concept that there may be multiple PAF receptors.
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Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Kinnaird
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D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D004224:Diterpenes; D046934:Ginkgolides; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007783:Lactones / Q000494:pharmacology; D020024:Leukotriene Antagonists; D007975:Leukotriene B4 / Q000494:pharmacology; D010477:Perfusion; D010654:Phenylbutyrates / Q000494:pharmacology; D010879:Piperazines; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002722:Chlorobenzenes
D004224:Diterpenes; D046934:Ginkgolides; D007211:Indoles; D007213:Indomethacin; D007783:Lactones; D020024:Leukotriene Antagonists; D007975:Leukotriene B4; D010654:Phenylbutyrates; D010879:Piperazines; D010972:Platelet Activating Factor; D013189:SRS-A; C060893:MK-886; D002722:Chlorobenzenes; C048269:FR 900452; C050033:L 649923; C045856:ginkgolide B