Increased airway reactivity in the guinea‐pig follows exposure to intravenous isoprenaline.

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.

Enhancement of airway reactivity to histamine by isoprenaline and related β‐adrenoceptor agonists in the guinea‐pig

“…Our observations confirm the principal findings reported by Morley and co-workers Mazzoni et al, 1987;Sanjar et al, 1990;Morley et al, 1991) tivity in anaesthetized guinea-pigs. However, some of our results differ and require some discussion.…”

“…This is at variance with the observations of Sanjar et al (1990) who observed no enhancement. The difference can perhaps be explained by inspection of our Figure 6a.…”

“…Recently, Morley and co-workers (Mazzoni et al, 1987;Sanjar et al, 1990) have reported that an i.v. infusion of ( ± )-isoprenaline in the anaesthetized guinea-pig enhanced the bronchoconstrictor effect of a fixed dose of bombesin, an effect prevented by bilateral vagotomy.…”

Exacerbation of Airway Hyperreactivity by (±)Salbutamol in Sensitized Guinea Pigs

“…More recently, it has been established that acute in travenous infusion of (±)isoprenaline induces airway hyperreactivity in guinea pigs (7), and this effect has been shown to extend to p2-selective sympathomimetics such as (± )salbutamol (8). Acutely, this property of (± )salbuta mol is masked by the bronchodilator action of (-)salbuta mol, but following sustained infusion of (±)salbuta mol over several days, increased sensitivity of the airways can be demonstrated to antigen (9) and to airway spas mogens (10).…”

Airway Smooth Muscle in Asthma Symptoms: Culprit but Maybe Innocent

“…Initial studies in that area begin in the late 1970s and have started by looking at the combined effect of spasmogens on different measures of lung function in animals (45,46,57,99,102,112,131,152,180,181,192,208,209,224,244), as well as in humans (49,68,97,101,110,156,158,194,202,240). Apart from an interactive synergism at the level of ASM contraction, many other factors can account for these in vivo interactive synergisms.…”