Airway reactivity to inhaled spasmogens 18-24 h after antigen-challenge in sensitized anaesthetized guinea-pigs.
The anaesthetized allergic guinea-pig was used to assess changes in airway reactivity to four different inhaled spasmogens: methacholine, 5-hydroxytryptamine (5-HT), histamine and the thromboxane A2 mimetic, 9,11-dideoxy-9 alpha,11 alpha-methano-epoxy-PGF2 alpha (U-46619). Reactivity was determined 18 to 24 h after challenge of ovalbumin-sensitized guinea-pigs with inhaled ovalbumin. This time coincides with the appearance of a late-phase bronchoconstriction in these animals. Sensitivity to the spasmogen was assessed from the concentration-response curve for the increase in pulmonary inflation pressure (PIP) in ovalbumin- and saline-challenged sensitized animals. When methacholine, 5-HT or histamine were the spasmogens there was no hyper-reactivity. The geometric mean EC50 values (i.e. the concentrations inducing half the maximum effect) obtained from the dose-response curves for methacholine (73 (42-129) and 94 (66-134) micrograms mL-1), 5-HT (1.5 (0.81-3.03) and 1.1 (0.51-2.24 micrograms mL-1) and histamine (39 (21-75) and 72 (32-162) micrograms mL-1) did not differ significantly (P > 0.05) between saline- and ovalbumin-challenged animals, respectively. However, when U-46619 was the spasmogen, ovalbumin-induced airway hyper-reactivity was observed as a leftwards shift of the concentration-response curve and the EC50 value for ovalbumin-challenged animals (8.1 (5.1-13) ng mL-1) was significantly (P < 0.05) less than the value for control animals (39 (21-75) ng mL-1). Our findings suggest that airway hyper-reactivity is not 'non-specific', but instead depends on the chosen spasmogen. The absence of hyper-reactivity with certain spasmogens was not a result of poor delivery, because all spasmogens caused a bronchoconstriction by the inhaled route. It was also not associated with the model because ozone has been shown to induce hyper-reactivity to inhaled methacholine and 5-HT. Because airway hyper-reactivity to both inhaled histamine and agonists at muscarinic receptors is regularly seen in man, the anaesthetized guinea-pig might not be the ideal model for assessing airway hyper-reactivity after antigen challenge and its modification by anti-asthma drugs.
Johnson
A
A
Division of Pharmacology, Welsh School of Pharmacy, University of Wales, Cardiff, UK.
Broadley
K J
KJ
D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001980:Bronchi / Q000187:drug effects*; D016535:Bronchial Hyperreactivity / Q000139:chemically induced*; D016085:Bronchoconstrictor Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D007114:Immunization; D008297:Male; D010047:Ovalbumin / Q000494:pharmacology*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D013997:Time Factors
D000336:Aerosols; D016085:Bronchoconstrictor Agents; D015842:Serine Proteinase Inhibitors; D010047:Ovalbumin