Arteriolar oxygen reactivity is inhibited by leukotriene antagonists

Experiments were performed to test the hypothesis that the arteriolar constriction produced by elevated oxygen tensions in the hamster cheek pouch is mediated by a leukotriene. To test this hypothesis, the diameter response of arterioles in superfused hamster cheek pouch preparations to stepwise increases in superfusion solution oxygen content was measured by video microscopy in the absence and 30 min after superfusion with solutions containing inhibitors of the synthesis or actions of leukotrienes. Oxygen-induced constrictions were inhibited in a dose-dependent fashion by two structurally distinct 5-lipoxygenase inhibitors (U 60257 and SC 43251) and two different leukotriene receptor antagonists (SKF 102922 and FPL 55712). Also, all four inhibitors tended to dilate the arterioles under low PO2 conditions. The inhibition of oxygen reactivity appeared to be selective in that arteriolar constrictions induced by topical application of phenylephrine were unaffected (SC 43251, SKF 102922, FPL 55717, and 30 microM U 60257) or only modestly reduced (100 microM U 60257) by the inhibitors. These data are consistent with the hypothesis that a leukotriene, or related compound, mediates arteriolar oxygen reactivity in the hamster cheek pouch.