Abstract
1. Intravenous infusion of (+/-) isoprenaline (1-100 micrograms kg-1 h-1) enhanced airway responses (resistance, RL; and compliance, Cdyn) to histamine (1.0-1.8 micrograms kg-1) and bombesin (100-240 ng kg-1), whereas airway responses to vagal stimulation remained unchanged. 2. Bilateral vagotomy before intravenous infusion of (+/-)isoprenaline (100 micrograms kg-1 h-1) prevented development of airway hyperreactivity to histamine or bombesin, yet vagotomy after infusion of isoprenaline was without effect. 3. Prior treatment with atropine (1 mg kg-1) did not influence the capacity of (+/-)isoprenaline (100 micrograms kg-1 h-1) to increase airway reactivity to bombesin. 4. Despite a 500-fold difference in spasmolytic potency in vivo, infusion of (+)isoprenaline (100 micrograms kg-1 h-1) or (-)isoprenaline (100 micrograms kg-1 h-1) increased reactivity of the airways to histamine or bombesin to a comparable extent. 5. Neither adrenaline (100 micrograms kg-1 h-1) nor forskolin (600 micrograms kg-1 h-1) increased reactivity of the airways to histamine or bombesin. 6. Intravenous infusion of dopamine (100 micrograms kg-1 h-1) or noradrenaline (100 micrograms kg-1 h-1) increased reactivity of the airways to histamine or bombesin. 7. Intravenous infusion of (+/-) propranolol (100 micrograms kg-1 h-1) increased reactivity of the airways to histamine or bombesin which was partially inhibited by bilateral vagal section. 8. Depletion of circulating platelets by lytic anti-platelet serum or concomitant infusion of an antagonist of platelet-activating factor (PAF), ginkgolide B (1 mg kg-1 h-1) did not diminish the capacity of (+/-)isoprenaline (100 micrograms kg-1 h-1) to induce hyperreactivity of the airways to histamine or bombesin. 9. These observations indicate that (+/-)isoprenaline can induce airway hyper-reactivity by a mechanism unrelated to beta-adrenoceptor activation, but which is dependent upon intact vagus nerves.