Actions of synthetic leukotrienes on platelets and blood vessels in the anesthetised pig: the release of a platelet derived vasodilator

The actions of leukotrienes (LT'a) C4, D4, E4 and F4 have been investigated in the perfused hind-limb of the anesthetized pig. In the blood perfused hind limb LTC₄, D₄ and E₄ increased the perfusion pressure in a dose-dependent fashion whereas LTF₄ decreased perfusion pressure. In the Tyrode perfused hind limb all LT's increased perfusion pressure (rank order potency (LTC₄ = LTD LTF₄). The actions of LTF₄ were not affected by a wide variety of pharmacological treatments, including indomethacin, methysergide and FPL-55712. The LT's aggregated porcine platelets (rank order potency LTC₄ > LTF₄ > LTD₄) and induced the release of a platelet-derived vasodilatory mediator. The results provide pharmacological evidence of specific leukotriene receptors and that leukotrienes can independently modulate blood flow. These data suggest that important interactions may occur between platelets, the arachidonate lipoxygenase products and platelet-derived substances in response to inflammatory stimuli in the cardiovascular system.