Maturational changes in responses of tissue and airway resistance to histamine.

We determined how postnatal maturation affects the relative contributions of airways and lung parenchyma to pulmonary resistance (RL) and whether there are developmental differences in their respective responses to constrictive agents. We studied open-chest ventilated anesthetized piglets of three ages: 2-4 days, 2-3 wk, and 10 wk. RL as partitioned into tissue (Rti) and airway (Raw) resistance by means of alveolar capsules under baseline conditions and after intravenous histamine. Postnatal maturation was associated with a progressive decline in RL, Rti and Raw and with an increase in the contribution of Rti and RL from 38 +/- 8% at 2-4 days to 72 +/- 2% at both 2-3 and 10 wk. Histamine caused RL to increase at all ages. When partitioned into Rti and Raw, the percent increase in Rti significantly exceeded that of Raw at both 2-4 days and 2-3 wk. In contrast, the percent increase in Raw significantly exceeded that of Rti at 10 wk. Administration of atropine before histamine in piglets aged 10 wk reduced the response of Rti and Raw to histamine. Histamine-induced responses of RL were blocked by prior H1-receptor blockade with pyrilamine (2 mg/kg). These results indicate that 1) the contribution of Rti and Raw to RL changes during maturation and that 2) contractile responses to exogenous histamine are manifest predominantly in most distal airways and lung parenchyma during early postnatal life; with advancing maturation there is greater contribution of airways to the increase in RL induced by histamine.