Prostaglandin synthesis inhibition restores hypoxic pulmonary vasoconstriction

Hypoxic pulmonary vasoconstriction in blood-perfused isolated dog lungs progressively diminishes with repeated hypoxic challenges. We investigated the role of prostaglandins in effecting the decay of the hypoxic response by using a double perfusion preparation that could separately perfuse the right and left lungs of a single dog. Degeneration of this response was reversed by the addition of prostaglandin (PG) synthesis inhibitors, aspirin, or indomethacin. Various PG's known to be produced by the lung (PGE1, PGE2, and PGF2alpha), were infused, and only PGE1 abolished hypoxic pulmonary vasoconstriction. Since other workers have shown that lungs can synthesize and release PG's in response to various stimuli, we postulate that PGE1 synthesis in isolated lungs may increase and thereby cause the degeneration of the hypoxic response. The addition of aspirin or indomethacin could inhibit the synthesis of PGE1 and thereby restore hypoxic pulmonary vasoconstriction.