Interactions of endotoxin, prostaglandins, and circulating cells upon pulmonary vascular resistance.

We studied the effects of endotoxin on total pulmonary vascular resistance (PVR) and hypoxic pulmonary vasoconstriction (HPV) in 24 isolated canine lung lobes. Group 1 lobes were perfused with whole blood; group 2 lobes with granulocyte/platelet depleted blood; group 3 lobes with whole blood and ibuprofen (12.5 mg/kg); group 4 lobes with granulocyte/platelet depleted blood and ibuprofen (12.5 mg/kg). All groups were otherwise treated in a similar manner and all received endotoxin (1 mg/kg) after baseline periods of normoxic and hypoxic ventilation. We found endotoxin increased PVR by 18% in group 1 and by 41% in group 2. Endotoxin administration inhibited HPV in group 1 but did not inhibit HPV in group 2. Ibuprofen administration prevented the increase in PVR and the loss of HPV caused by endotoxin. We conclude that endotoxin administration causes release of a lung-derived vasoconstrictor, but this is obscured by concomitant release of a granulocyte/platelet associated vasodilator. Our data also suggest that granulocytes or platelets may modulate baseline PVR by producing a nonprostaglandin vasodilator.