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 nordihydroguaiu retic acid (NDGA), a lipoxygenase inhibitor, on hypoxic pulmonary vaso constriction and on immunoreactive leukotriene C4 (i-LTC4) levels in l ung lymph, perfusate and bronchoalveolar lavage (BAL) fluid in isolate d, indomethacin treated, sheep lungs perfused with blood at a constant flow of 100 ml/kg/min. The protocol consisted of two randomized perio ds with inspired O2 concentration either 28.2 or 4.2%. Five groups of lungs were studied with calculated NDGA concentrations of 0 to 1300 mu M. At the end of each period, i-LTC4 was measured in lung lymph, perfu sate and BAL. NDGA levels were also measured. Consistent with our prev ious 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 t imes lower than those causing inhibition of hypoxic vasoconstriction. These NDGA concentrations also inhibited vasomotor responses to KCl, s erotonin and PGF2alpha suggesting nonspecificity. These observations a re not consistent with mediation of hypoxic vasoconstriction by i-LTC4 .