EFFECTS OF NORDIHYDROGUAIURETIC ACID ON SULFIDOPEPTIDE LEUKOTRIENE ACTIVITY AND HYPOXIC PULMONARY VASOCONSTRICTION IN THE ISOLATED SHEEP LUNG

Sulfidopeptide leukotrienes have been proposed as mediators of hypoxic pulmonary vasoconstriction. We studied the effects of nordihydroguaiuretic acid (NDGA), a lipoxygenase inhibitor, on hypoxic pulmonary vasoconstriction and on immunoreactive leukotriene C4 (i-LTC4) levels in lung lymph, perfusate and bronchoalveolar lavage (BAL) fluid in isolated, indomethacin treated, sheep lungs perfused with blood at a constant flow of 100 ml/kg/min. The protocol consisted of two randomized periods with inspired O2 concentration either 28.2 or 4.2%. Five groups of lungs were studied with calculated NDGA concentrations of 0 to 1300 muM. At the end of each period, i-LTC4 was measured in lung lymph, perfusate and BAL. NDGA levels were also measured. Consistent with our previous findings (10) , hypoxia did not increase i-LTC4 levels in lymph, perfusate or BAL fluid. Although NDGA decreased i-LTC4 in perfusate in a dose-dependent manner, it did so at concentrations which were ten times lower than those causing inhibition of hypoxic vasoconstriction. These NDGA concentrations also inhibited vasomotor responses to KCl, serotonin and PGF2alpha suggesting nonspecificity. These observations are not consistent with mediation of hypoxic vasoconstriction by i-LTC4.