The Influence of Drugs and Other Factors on Inactivation of Prostaglandin E2 by the Rat Isolated Perfused Lung

1. The mechanisms responsible for inactivating prostaglandin E₂ (PGE₂) in the rat isolated lung were saturated by high rates of arterial presentation of the prostaglandin. 2. Lungs from normotensive females, and from males of the New Zealand hypertensive strain, inactivated PGE₂ less readily than did those from normotensive males. 3. Increasing the perfusion rate or pre-treating animals with probenecid or cycloheximide reduced inactivation of PGE₂. Treatment with cycloheximide plus probenecid did not however reduce inactivation to a greater extent than did cycloheximide alone. 4. Pregnancy or administration of hydrocortisone increased pulmonary removal of PGE₂ whereas adrenalectomy reduced it. 5. Thus the rate of inactivation of PGE₂ in this species may depend both on the activity of an initial active transport process and also on the levels of catabolising enzymes. The latter may be of greatest importance when pulmonary artery concentrations of PGE₂ are low with the transport mechanism assuming greater significance when they are high. The rate of removal is also dependent on sex, genotype, steroidal status, pregnancy and pulmonary flow.