Increased airway reactivity in the guinea-pig follows exposure to intravenous isoprenaline.
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.
Sandoz Ltd, Basel, Switzerland.
S
S
Sanjar
A
A
Kristersson
L
L
Mazzoni
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J
Morley
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E
Schaeublin
D000403:Airway Resistance / Q000187:drug effects*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism; D001839:Bombesin / Q000494:pharmacology; D001993:Bronchodilator Agents / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D004298:Dopamine / Q000008:administration & dosage / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology*; D007275:Injections, Intravenous; D007545:Isoproterenol / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors; D011433:Propranolol / Q000008:administration & dosage / Q000494:pharmacology; D011817:Rabbits; D014628:Vagotomy; D014630:Vagus Nerve / Q000502:physiology
D001993:Bronchodilator Agents; D010972:Platelet Activating Factor; D005576:Colforsin; D001285:Atropine; D006632:Histamine; D011433:Propranolol; D007545:Isoproterenol; D001839:Bombesin; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine