Increased pulmonary vascular resistance and permebility due to arachidonate metabolism in isolated rabbit lungs

Liberation and metabolism of arachidonic acid may be the common final pathway of different stimuli on the pulmunary vascular bed. In a model of isolated, ventilated rabbit lungs, perfused with krebs Henseleit albumin buffer in a recirculating system, changes of pulmonary vascular resistance and of vascular permeability are monitored continously. The addition of free arachidonic acid or of the Ca-ionophore A 23187 to the perfusion fluid consistently evokes a biphasic increases in vascular resistance as well as an initially reversible increase in vascular permeability, followed by pulmonary edema. Both phases of increased vascular resistance are completely suppressed by inhibition of the cyclooxygenase, decreased to a large degree by inhibitors of thromnoxane synthetase, and markedly augmented by short preincubation of arachidonic acid with ram seminal vescular microsomes and by sulfhydryl reagents. The increased pulmonary vascular permeability is augmented by inhibition of cyclooxygenase and reduced by simulteneous lipoxygenase inhibition. Antagonists of histamine, serotonin and sympathic or parasympathic activity do not have any influence.PG F_2α, TxB E₂ and PG I₂ alter the pulmonary vascular resistance, but do not increase vascular permeability.In inclusion, increased availability of free arachidonic acid evokes a rise in pulmonary vascular resistance, which can be ascribed to cyclooxygenase products, especially to thromboxane, and causes a rise in vascular permeability which can be ascribed to lipoxygenase products.The findings may be related to acute pulmonary lesions with increase in vascular resistance and with vascular leakage.