INHIBITION OF PLATELET-ACTIVATING FACTOR-INDUCED RESPONSES IN GUINEA-PIG ISOLATED HEART BY A PAF-ANTAGONIST, WEB-2086

The study was undertaken to investigate the inhibitory activity of a p latelet-activating factor (PAF) antagonist, WEB 2086, against PAF-indu ced cardiac responses in guinea-pig isolated hearts. The capacity of P AF to elicit cardiovascular changes in a number of different species i n vivo and in vitro has been reported. Bolus injection of PAF (50 pmol ) elicited cardiovascular changes characterized by persistent and irre versible increase in coronary perfusion pressure (Cpp) and a decrease in cardiac developed tension (Cdt). Concomitanly, PAF triggered releas e of immunoreactive (ir) thromboxane B2 (TxB2) and immunoreactive (ir) leukotriene C4 (LTC4). WEB 2086 (0.03, 0.1 and 0.3 muM) antagonized P AF-induced increases in Cpp and decreases in Cdt in a reversible and c oncentration-dependent manner. At a concentration of 0.3 muM, WEB 2086 significantly reduced LTC4 and TxB2 release. No significant inhibitor y effect was observed on the LTC4 and U44069-induced increase in Cpp. In conclusion, the present studies suggest that WEB 2086 is a potent, reversible and a selective PAF antagonist.