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.
D000336:Aerosols; D000403:Airway Resistance; D000818:Animals; D004285:Dogs; D006632:Histamine / Q000097:blood; D006633:Histamine Antagonists; D006636:Histamine Release / Q000187:drug effects*; D008168:Lung / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D008170:Lung Compliance; D008407:Mast Cells / Q000166:cytology / Q000378:metabolism*; D011433:Propranolol / Q000494:pharmacology; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology*
D000336:Aerosols; D006633:Histamine Antagonists; D003189:p-Methoxy-N-methylphenethylamine; D006632:Histamine; D011433:Propranolol