DIFFERENTIAL ACTIONS OF PLATELET-ACTIVATING-FACTOR (PAF) RECEPTOR ANTAGONISTS ON THE VASODILATOR AND VASOCONSTRICTOR EFFECTS OF PAF IN THE RAT PERFUSED HEART

Selectivity for blocking the coronary vasodilator and vasoconstrictor effects of platelet-activating factor (PAF) in the rat perfused heart was observed with different PAF antagonists. CV-6209 showed selectivity for blocking the vasodilator effect of PAF and a higher concentration (10 fold) was required to block the vasoconstrictor effect. The remaining PAF antagonists (FR-900452, WEB 2086 and BN-50739) showed selectivity for blocking the vasoconstrictor effect of PAF (10, 200 and 1000 fold respectively). A combination of low concentrations of CV-6209 (10nM) with FR-900452 (5-mu-M) or WEB 2086 (0.5-mu-M) was effective in blocking both the vasodilator and vasoconstrictor effects of PAF. CV-6209 and WEB 2086 did not affect the vasodilator action of leukotriene B4 (LTB4) and the vasoconstrictor action of LTC4 and LTD4. Our results support the hypothesis that the functionally opposite effects of PAF in the rat perfused heart may be mediated by different PAF receptor subtypes.