Effect of Maturation on Topographic Distribution of Bronchoconstrictor Responses in Large Diameter Airways of Young Swine

We studied the effect of maturation on the topographic distribution of airway constriction in Generations 0 (trachea) through 6 in fourteen 2-wk-old swine (2ws) and sixteen 10-wk-old swine (10ws) in vivo and in excised airways from seven 2ws and seven 10ws in vitro. Animals were anesthetized with chloralose-urethane and received beta-adrenergic blockade and vagotomy prior to generation of random-order, does-response curves with i.v. methacholine (MCh) and histamine (His) or serotonin (5HT) given intravenously. Lung resistance (Rl) was measured, and airway diameter was assessed by tantalum bronchograms obtained at functional residual capacity for each dose of agonist. Baseline Rl was substantially greater in 2ws (48 to 62 cm H2O/L/s) than in 10ws (9 to 11 cm H2O/L/s; p < 0.001 for all groups). Intravenous infusion of 10−6 mol/kg MCh caused a 416 ± 110% increase in Rl in 2ws and a 314 ± 32% increase in Rl in 10 ws (p = NS); airway diameter (Daw) decreased by 10 ± 1% (Generation 2) to 27 ± 4% (Generation 6) in 2ws and from 8 ± 2 (Generation 2) to 17 ± 4% in 10ws. Intravenous infusion of 10−6 mol/kg His caused a 513 ± 85% increase in Rl in 2ws and a 276 ± 17% increase in Rl in 10 ws (p < 0.05). In contrast to MCh, His was a potent constrictor agonist in Generation 4 airways (15 ± 3% decrease in Daw) and Generation 6 airways (27 ± 4% decrease in Daw) of 2ws but not in Generation 4 (3 ± 1% decrease in Daw; p < 0.05 versus 2 ws) or Generation 6 airways (13 ± 5% decrease in Daw; p < 0.06 versus 2ws) of 10ws. H2-receptor blockade with cimetidine did not alter the contractile properties of trachea, Generation 2 or Generation 4 airways in either 2ws or 10ws. The response to 5HT was not substantial in either central or peripheral airways in either 2ws or 10ws. We conclude that the relative distribution of contractile responses to His and MCh change during maturation from 2ws to 10ws. Histamine-induced airway narrowing in vivo relative to MCh in the major diameter bronchi decreases in 10ws versus 2ws by a mechanism not related to topographic redistribution of H2-receptors during maturation.