Abstract
We have investigated the effects of mediators released from blood cell fraction supernatant, white blood cells (WBCs), platelet suspension (Pls) and a mixture of white blood cells and platelets (WBCs+PLs) on the pulmonary vascular bed of the rabbit, using intact and denuded isolated pulmonary arterial rings. WBCs, Pls and WBCs+PLs supernatant produced a volume-dependent increase in the pulmonary arterial tension in both intact and denuded pulmonary arterial rings. Removal of endothelium augmented the increase in pulmonary arterial tension attributable to Pls and WBCs+PLs but not that to WBCs. Indomethacin, a cyclo-oxygenase inhibitor, and prednisolone, a phospholipase A(2) inhibitor, did not significantly alter the presser responses of WBCs, Pls or WBCs+PLs supernatant in intact or denuded rings. On the other hand, the effects of WBCs, Pls and WBCs+PLs supernatant in intact and denuded rings were attenuated by mepyramine, a histamine H-1 receptor antagonist. They were totally abolished by mepyramine and methysergide, a 5-MT2 receptor antagonist. These results suggest that during inflammation, or after activation of white blood cells, the main bioactive mediators released are histamine and serotonin, which reach the lung and cause a powerful pulmonary vasoconstriction. Furthermore, intact endothelium protects the pulmonary vessels against enhanced presser effects induced by the released vasoactive agents upon stimulation of white blood cells. Under the conditions of the present study, arachidonic acid metabolites and platelet activating factor are probably not involved in mediating the presser effects of stimulated WBCs in rabbit lung. (C) 1998 Chapman & Hall Ltd.