PMID: 3034369Apr 1, 1987

Antagonism of vasoconstriction induced by platelet-activating factor in guinea-pig perfused hearts by selective platelet-activating factor receptor antagonists

British Journal of Pharmacology
P J Piper, A G Stewart


Platelet-activating factor (Paf) is a potent coronary vasoconstrictor in rat, guinea-pig, dog and pig. The present study investigated the mechanism and duration of Paf in guinea-pig isolated, Krebs-perfused hearts. Dose-related and sustained decreases in cardiac contractility and increases in coronary perfusion pressure were elicited by bolus doses of Paf (0.3-100 pmol). Platelet-activating factor (30 pmol) induced increases in the production of immunoreactive thromboxane B2 (TXB2), leukotriene B4 (LTB4) and LTC4, but not 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha). In addition, the release of leukotriene-like material following Paf was observed using on-line superfusion bioassay. The coronary vasoconstrictor actions of Paf were partially antagonized by the leukotriene receptor antagonist, FPL 55712 (1.9 microM), or by indomethacin (2.8 microM). The combined use of these compounds did not result in further significant inhibition. The Paf receptor antagonists, BN 52021 (30 microM) and L 652, 731 (10 microM), antagonized both the increase in coronary perfusion pressure and the decrease in cardiac contractility induced by Paf (10-100 pmol) in a surmountable and relatively selective manner. The effects of a bolus dose of 100 ...Continue Reading


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