Distribution oand pharmacological release of histamine in canine lung in vivo

We have examined the physiological effects of stored mediators released from airways by compound 48/80 aerosols in anesthetized dogs. In 13 dogs, both mast cell numbers and tissue histamine were related inversely to bronchial internal diameter (P less than 0.0001). Compound 48/80 aerosols degranulated mast cells and decreased histamine content (-29.0 +/- 10.0%; mean +/- SE) in 5-10 mm bronchi, but not in 3-4 mm bronchi or lung parenchyma. This was associated with increased plasma histamine (31.8 +/- 18.4 ng/ml), increased airflow resistance (Rrs: + 452 +/- 257%), decreased lung compliance (-28 +/- 10%), and decreased arterial blood pressure (-41 +/- 6.5%) at 2 min. The increased Rrs was reversed by beta-adrenergic agonists, indicating it was caused by bronchial smooth muscle contraction; prevented by chlorpheniramine, indicating it was caused by histamine action on H1-receptors; and augmented and prolonged by propranolol, suggesting that histamine triggered sympathetic mechanisms which modulated the effect of 48/80. This experimental approach permits the study of mechanisms in vivo which may be involved in the sequence of reactions initiated by antigen-IgE interaction. However, the latter involve not only stored mediators, but also unstored mediators, neural reflexes, and complex cellular interactions.