Role of H1 and H2 receptors in increased small airways resistance in the dog

The relative importance of H1 and H2 receptors to central and peripheral airways resistance in the anesthetized intact dog lung were determined through the use of pharmacologically specific antagonists during graded intravenous infusions of histamine. The indirect effects of infused histamine were also tested via alpha and beta adrenergic blockade (alpha + beta blk) and post-ganglionic parasympathetic blockade (vagal blk). We measured pulmonary resistance (RL), dynamic compliance (Cdyn), thoracic gas volume (Vtg), and partitioned oscillatory pulmonary resistance (RLosc) into a peripheral (Rp) and central component with an intrabronchial catheter. Infused histamine caused a significant increase in RL, primarily the result of the increase in Rp, with substantial dose-dependent reductions in Cdyn, and increases in Vtg. These effects were not altered by vagal blk, were increased by alpha + beta blk, and were completely prevented by H1 receptor blockade, but not by H2 receptor blockade. We conclude that histamine infusion causes bronchoconstriction in the canine lung, primarily in peripheral airways (less than 3 mm diameter), by its direct action on H1-type receptors.