Role of eicosanoids in hypoxic vasoconstriction in isolated lamb lungs

To determine the role of eicosanoids in hypoxic pulmonary vasoconstriction, we studied 42 isolated, blood-perfused lamb lungs during normoxia and hypoxia. We used the lung micropuncture technique to measure microvascular pressures in 20- to 80-micron diameter arterioles and venules and estimated segmental vascular resistance. In separate experiments, lungs were untreated or treated with either indomethacin (a cyclooxygenase inhibitor), Dazmegrel (a thromboxane synthetase inhibitor), SQ 29548 (a thromboxane receptor blocker), FPL 57231 (a leukotriene receptor blocker), or U 60257 (a 5'lipoxygenase inhibitor). In control untreated lungs both pulmonary arteries and veins constricted during hypoxia. Addition of indomethacin, Dazmegrel, or SQ 29548 to the perfusate resulted in abolition of venous constriction during hypoxia but enhancement of arterial constriction. FPL 57231 or U 60257 resulted in complete abolition of the pulmonary hypoxic vasoconstrictor response. Our results indicate that during hypoxia, leukotrienes mediate arterial and venous constriction with thromboxane A2 being necessary for venous constriction. We conclude that the interaction between 5'lipoxygenase and cyclooxygenase products of arachidonic acid results in the characteristic pulmonary hypoxic vasoconstrictor response in isolated, perfused lamb lungs.