Mechanisms of vascular actions of PAF.

The vascular actions of platelet-activating factor (PAF) in the coronary circulation in vitro (rat, guinea-pig) and the intracranial circulation in vivo in the anaesthetized pig have been examined. PAF elicited platelet-independent coronary vasoconstrictor responses which were associated with the release of vasoactive amounts of cyclo-oxygenase and lipoxygenase products. Vasoconstrictor responses in rat hearts showed a greater dependence on the release of leukotriene (LT) C4 than those in guinea-pig hearts. In addition, the latter species was considerably more sensitive to the coronary vasoconstrictor actions of PAF. Intra-arterial administration of PAF in the pig evoked biphasic changes in intracranial blood flow comprising a transient increase followed by prolonged decrease. Indomethacin treatment inhibited the decreases in blood flow whereas the transient increases in flow became more pronounced. These results suggest that PAF acts, as least partly, via the release of vasoactive arachidonic acid metabolites. The potency and duration of PAF-induced vasoconstriction suggest a role for this pro-inflammatory phospholipid in the reduction of cerebral and coronary blood flow in pathological conditions.