Pulmonary vascular effects of endotoxin in leukopenic dogs

We have demonstrated previously that in the dog, small doses of endotoxin abolish the pulmonary vasoconstrictor reponse to hypoxia, apparently by stimulating the production of a vasodilator prostaglandin. We previously ruled out platelets as mediators of this endotoxin effect. To evaluate leukocytes as possible mediators, we rendered dogs leukopenic by means of a leukocyte antiserum. However, this did not modify the inhibitory effect of endotoxin on hypoxic pulmonary vasoconstriction. Hence, neither leukocytes nor platelets appear to mediate the endotoxin effect. In the near absence of both platelets and leukocytes, the endotoxin effect can be prevented by inhibiting prostaglandin synthesis with meclofenamate. This suggests that endotoxin prevents hypoxic pulmonary vasoconstriction by acting on the systemic circulation or on the lung (possibly directly on the pulmonary blood vessels) to stimulate the production of a vasodilator prostaglandin.