EFFECT OF MATURATION ON HISTAMINE-INDUCED AIR-FLOW OBSTRUCTION AND AIRWAY MICROVASCULAR LEAKAGE IN GUINEA-PIG AIRWAYS

To study the effect of maturation on histamine-induced airflow obstruction and airway microvascular leakage, we measured concomitant changes in lung resistance (R(L)) and in extravasation of Evans Blue dye in the airways of anesthetized immature (aged 14 +/- 2 days) and adult guinea pigs (aged 60 +/- 12 days). R(L) was measured for 6 min after iv. histamine (0, 5, 15, 30 and 50-mu-g/kg). For comparison, responses after 1-mu-g/kg substance P were also examined. After measurement of R(L), microvascular leakage in trachea, main bronchi, and proximal and distal intrapulmonary airways was also examined in the same animal. Immature animals required a larger dose of histamine than adults to achieve a similar degree of maximal bronchoconstriction after histamine. In contrast, equal doses of histamine (15 and 30-mu-g/kg) induced a significantly greater extravasation of dye in immature airways in both proximal and distal intrapulmonary airways, although not in trachea or main bronchi. Substance P did not cause any age-related differences in dye extravasation at any airway level. These results suggest that i.v. histamine specifically causes a greater degree of airway microvascular leakage in peripheral airways but induces less smooth muscle contraction in the airways of immature guinea pigs than in the airways of adult animals.