Role of H 1 and H 2 receptors in increased small airways resistance in the dog

Abstract

The relative importance of H 1 and H 2 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 (α + β blk) and post-ganglionic parasympathetic blockade (vagal blk). We measured pulmonary resistance (R L), dynamic compliance (C dyn), thoracic gas volume (V tg), and partitioned oscillatory pulmonary resistance (R Losc) into a peripheral (R p) and central component with an intrabronchial catheter. Infused histamine caused a significant increase in R L, primarily the result of the increase in R P, with substantial dose-dependent reductions in C dyn, and increases in V tg. These effects were not altered by vagal blk, were increased by α + β blk, and were completely prevented by H 1 receptor blockade, but not by H 2 receptor blockade. We conclude that histamine infusion causes bronchoconstriction in the canine lung, primarily inperipheral airways (< 3 mm diameter), by its direct action in H 1-type receptors.