In vitro responses of equine small airways and lung parenchyma

In vitro responses of equine small peripheral airways (SA) and lung parenchyma (LP) were studied. We examined their contractile and relaxant responses and investigated effects of histamine, and endogenous prostanoids as these mediators may play a role in development or recurrent airway obstruction in horses (heaves). SA and LP electrical field stimulation (EFS) induced nearly maximal and partial frequency-dependent contractions, respectively. These contractions were virtually abolished in SA but only partially inhibited in LP by atropine (ATR) and tetrodotoxin (TTX). Methacholine (MCh) contracted SA with a 5-fold higher potency and greater maximal tension than LP. In SA but not in LP, a large augmentation of EFS responses at 1-4 Hz was produced by both meclofenamate, a cyclooxygenase blocker and 3 microM histamine. We conclude that: (1) excitatory input from cholinergic nerves largely determines SA tone, but has minor effect in LP; (2) in SA endogenous inhibitory prostanoids modulate contractile response to nerve stimulation; and (3) inhibition of cyclooxygenase and histamine greatly potentiate responses to nerve stimulation in SA. These data are consistent with the hypothesis that, in horses with heaves, histamine release and an altered prostanoid profile contribute to cholinergically mediated SA obstruction.