Citric acid airway constriction in dogs with hyperreactive airways

To understand the mechanisms underlying the bronchoconstrictor response to 10% citric acid administered for 5 min in Basenji-Greyhound (BG) dogs, we evaluated the protection afforded by atropine (0.2 and 0.4 mg/kg iv) and by aerosols of isoproterenol (1 mg/ml) and cromolyn sodium (20 mg/ml). In untreated dogs, citric acid increased pulmonary resistance by 4.6- to 11.5-fold and decreased dynamic compliance (Cdyn) to 45-55% of the control response. Isoproterenol and cromolyn sodium significantly reduced the response, whereas atropine did not. Moreover we have demonstrated in the arterial plasma of these dogs a slow-reacting substance (SRS) after, but not before, citric acid challenge. This SRS exhibits both pharmacologic properties and chemical characteristics similar to leukotrienes. We conclude that mediators of immediate-type hypersensitivity rather than reflex mechanisms play a dominant role in the production of airway constriction during citric acid (5-min) challenge in BG dogs.