Pulmonary and cardiovascular changes in hyperreactive rats from citric acid aerosols

Administration of aerosols of citric acid to anesthetized spontaneously breathing hyperreactive rats produced reversible increases in respiratory rate (f) and pleural pressure (Ppl) accompanied by hypotension and bradycardia. In contrast, Fischer rats, which do not have bronchial hyperreactivity, failed to respond to citric acid aerosols. The effects of various treatments on citric acid-induced changes in f, Ppl and blood pressure were studied. Vagotomy, cromolyn sodium (1 and 10 mg/kg iv), mecamylamine, (2 mg/kg iv), FPL-55712 (3 mg/kg iv), and BW 755C (10 mg/kg iv) inhibited markedly the responses to citric acid, whereas atropine (2 mg/kg iv) produced weak inhibition. Methysergide (1 mg/kg iv), indomethacin (1 mg/kg iv), and a prostanoid antagonist, L-640,035, (5 mg/kg iv) were completely ineffective. The results suggest that citric acid-induced bronchoconstriction in hyperreactive rats may be reflex mediated and that leukotrienes may be involved in the response.