Pulmonary microvascular effects of arachidonic acid metabolites and their role in lung vascular injury.

Arachidonic acid metabolites produced by cyclooxygenase and lipoxygenase pathways affect pulmonary transvascular fluid and protein fluxes after pulmonary microvascular injury. Some of these products may contribute to the increase microvascular endothelial permeability whereas others may increase pulmonary microvascular filtration pressure. Prostaglandin (PG) E2, PGF2 alpha and cyclic endoperoxides increase microvascular pressure and thus increase the transvascular fluid filtration rate. Thromboxanes increase microvascular pressure and in addition may promote neutrophil adherence to endothelium and platelet aggregation, whereas prostacyclin has opposing actions. The cysteine-containing leukotrienes (LTs) (LTC4, LTD4, and LTE4) increase pulmonary microvascular pressure via a thromboxane-mediated mechanism, and LTB4 may increase pulmonary vascular permeability. Arachidonic acid metabolites do not appear to alter directly pulmonary endothelial membrane permeability but may contribute to the increased permeability by their actions on blood-formed elements. The pulmonary vasoconstrictor arachidonic aid metabolites increase microvascular hydrostatic pressure and may thereby enhance the degree of pulmonary edema.