Leukotriene synthesis and receptor blockers block hypoxic pulmonary vasoconstriction.
We hypothesized that leukotrienes are involved in hypoxic pulmonary vasoconstriction, since they are pulmonary vasoconstrictors and cells capable of producing leukotrienes are located in the lung near resistance vessels. We investigated in isolated perfused rat lungs whether three structurally unrelated blockers [diethylcarbamazine citrate (DEC), U-60257, and FPL 55712] of leukotriene synthesis or action block hypoxic pulmonary vasoconstriction. DEC blocked ongoing and subsequent hypoxic pressor responses while minimally affecting the angiotensin II pressor response. The inhibition of the hypoxic pressor response by DEC was not affected by cyclooxygenase or H1-receptor blockers. Potassium-induced vasoconstriction, which is dependent on calcium entry, was largely blocked by verapamil but not by DEC, suggesting that DEC was not acting primarily as a calcium-entry blocker. U-60257 blocked the hypoxic pressor response without inhibiting the pressor response to angiotensin II or potassium chloride. FPL 55712, a leukotriene end-organ blocker, in a dose which inhibited vasoconstriction caused by exogenous leukotriene C4, inhibited the pressor response to hypoxia but not to angiotensin II. We conclude that leukotriene inhibitors preferentially inhibit hypoxic pulmonary vasoconstriction in isolated perfused adult rat lungs.
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002867:Chromones / Q000494:pharmacology; D004049:Diethylcarbamazine / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology / Q000031:analogs & derivatives; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D010100:Oxygen / Q000097:blood*; D011189:Potassium Chloride / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000096:biosynthesis*; D014661:Vasoconstriction / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology
D002867:Chromones; D013189:SRS-A; D000804:Angiotensin II; D008469:Meclofenamic Acid; D011189:Potassium Chloride; C006312:FPL 55712; D014700:Verapamil; D011464:Epoprostenol; C035296:piriprost; D010100:Oxygen; D004049:Diethylcarbamazine