PAF-acether induced cardiac dysfunction in the isolated perfused guinea pig heart.
PAF-acether (1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine) has been implicated in a variety of inflammatory and ischaemic disorders (e.g., myocardial ischemia, anaphylactic shock). Recently, the peptide leukotrienes (i.e., LTC4, LTD4) have been shown to mediate the increase in coronary vascular resistance induced by PAF-acether in the isolated perfused rat heart. In isolated perfused guinea pig hearts, PAF-acether produced a dose-dependent increase in coronary perfusion pressure (CPP) and a decrease in contractile force (CF). At 50 pmol/l, PAF increased CPP by 13 +/- 3 mm Hg and decreased CF by 47 +/- 12% in 8 hearts. Radioimmunoassay of the coronary effluent did not detect peptide leukotrienes or thromboxane B2 (TxB2) in response to PAF. Addition of a specific PAF-acether receptor antagonist, CV-6209 (25 nmol/l), blocked the increase in coronary perfusion pressure and decrease in contractile force. OKY-1581 (400 nmol/l), a thromboxane synthetase inhibitor or LY-171,883 (7.3 mumol/l) a leukotriene D4 receptor antagonist, failed to prevent the increase in CPP or the decrease in CF. These data indicate that the PAF-acether induced increase in CPP is not mediated by the peptide leukotrienes or thromboxane A2 (TxA2). Possible mechanisms for the increase in CPP induced by PAF-acether in the isolated perfused guinea pig heart include a direct receptor mediated constriction of coronary resistance vessels, release of a non-eicosanoid coronary constrictor as a mediator of the response, or via enhancement of coronary microvascular permeability.
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107.
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Lefer
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Lefer
D000818:Animals; D003331:Coronary Vessels / Q000502:physiology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008689:Methacrylates / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D011863:Radioimmunoassay; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D014661:Vasoconstriction
D008689:Methacrylates; D010972:Platelet Activating Factor; C031517:2-methyl-3-(4-(3-pyridinylmethyl)phenyl)-2-propenoic acid; D013930:Thromboxane-A Synthase