Effect of maturation on airway plasma exudation induced by eicosanoids in guinea pig

Abstract

Airway reactivity to bronchoconstrictor mediators changes with age. We studied the effects of maturational change on airway responses induced by a thromboxane A 2 mimetic, U-46619 (2, 6 and 20 nmol/kg; i.v.), leukotriene D 4 (0.6 and 2 nmol/kg; i.v.) or vehicle (0.9% NaCl; i.v.) in immature (196 ± 3 g: 2 weeks) and adult guinea pigs (512 ± 5 g: 11 weeks). In the same animals, we measured both lung resistance ( R L) to monitor airflow obstruction and extravasation of Evans Blue dye (20 mg/kg) to quantify airway plasma exudation. For a comparison, changes in R L in response to acetylcholine (5, 15 and 50 nmol/kg; i.v.) were also examined in both age groups. The order of potency to induce an increase in R L did not change with age (leukotriene D 4 > U-46619 > acetylcholine). In immature animals, the peak R L after U-46619 (2, 6 and 20 nmol/kg; P < 0.05, P < 0.005 and P < 0.01, respectively) and leukotriene D 4 (2 nmol/kg; P < 0.01) was significantly higher than in adult animals. U-46619 and leukotriene D 4 produced significant extravasation of Evans Blue dye in both immature and adult animals. The order of potency to induce extravasated dye also did not change with age (leukotriene D 4 > U-46619). The amount of extravasation of Evans Blue dye after U-46619 (6 and 20 nmol/kg) and leukotriene D 4 (0.6 and 2 nmol/kg) was significantly smaller in immature animals than adults at all airway levels. We conclude that U-46619 and leukotriene D 4 administered intravenously caused a smaller degree of airway plasma exudation, but induced a greater airflow obstruction in the airways of immature guinea pigs, compared to airways of adult animals.