Leukotriene Synthesis by Isolated Perinatal Ovine Intrapulmonary Vessels Correlates with Age-Related Changes in 5-Lipoxygenase Protein

Abstract

Leukotrienes (LT) are potent vasoconstrictors in the pulmonary circulation. We have investigated the synthesis of LTC4by intrapulmonary arteries and veins of perinatal lambs. Paired vessels of near-term fetal 146 ± 2- and 2- to 7-day-old newborn lambs (eachn= 7), were incubated for 10 min at 37°C in baseline, with 1 μmol/L A32187 or 0.1 mmol/L arachidonic acid. Produced leukotriene C4was assayed from media by ELISA. Baseline production of leukotriene (ng/mg tissue, means ± SEM) by vessels for arteries was 0.006 ± 0.001 and 0.059 ± 0.009 for fetus and newborn, respectively. In veins, the values were 0.013 ± 0.003 and 0.073 ± 0.007 for fetus and newborn, respectively. On stimulation with the calcium ionophore A23187, production by arteries increased 25-fold in the fetus, but 4-fold in the newborn. The corresponding values for stimulated veins were 37-fold and 9-fold in fetus and newborn, respectively. Generally, production by veins was greater than production by the matching arteries. In all instances, the fetal vessels produced less leukotrienes than the newborn vessels. Western analysis of stimulated and unstimulated vessel membrane protein showed greater expression of 5-lipoxygenase in veins than in arteries (P< 0.05). Our data show that veins produce more LTC4due to greater expression of 5-lipoxygenase in the vessels and thus suggest that veins of perinatal lamb lungs may be more susceptible to LT-induced vasoreactivity in the perinatal pulmonary circulation. We speculate that a higher production of LTC4by fetal veins may be necessary to maintain a high venous tone in fetal lungs.