Arachidonate raises vascular resistance but not permeability in lungs of awake sheep.

Prostaglandins have been implicated as mediators of pulmonary hypertension in a variety of reactions, but the agents responsible for pathological increases in lung vascular permeability have not been determined. To test the hypothesis that products of arachidonic acid metabolism produce pulmonary vasoconstriction and alter lung vascular permeability, we infused purified sodium arachidonate (25-100 micrograms . kg-1 . min-1) into chronically instrumented unanesthetized sheep prepared for collection of lung lymph. Arachidonate produced dose-related increases in pulmonary artery pressure and lung lymph flow with corresponding decreases in the lymph-to-plasma protein concentration ratio. Lung lymph responses were like those caused by mechanically elevating left atrial pressure. Infusion of indomethacin or sodium eicosatetraynoate inhibited hemodynamic and lung lymph responses to arachidonate. We conclude a) that arachidonate must be converted to prostaglandin cyclic endoperoxides to produce pulmonary hypertension and increased flow of protein-poor lung lymph and b) that under normal conditions, no detectable increase in lung vascular permeability results from either arachidonate itself or the combined products of arachidonate metabolism via cyclooxygenase and/or lipoxygenase.