Airway Hyperresponsiveness in Anaesthetised Guinea‐Pigs 18–24 Hours after Antigen Inhalation Does Not Occur with All Intravenously Administered Spasmogens

Abstract

Actively sensitised guinea-pigs were exposed to inhalation challenges with ovalbumin aerosol (macro-and microshock) and airway responsiveness to six intravenously administered spasmogens was evaluated 18 to 24 hr later in the anaesthetised animal. An increase in airway sensitivity was defined as a significant leftward shift of the dose-response curve when compared with saline-challenged control sensitized animals. After ovalbumin-macroshock (I% ovalbumin for 2 min. with mepyramine cover against fatal anaphylaxis), airway hyperresponsiveness was seen to 5-HT, the thromboxane A2-mimetic, U-46619, and bradykinin but not to methacholine, histamine or substance I? A similar pattern was seen after ovalbumin-microshock (0.01% ovalbumin for 60 min.). with induction of airway hyperreactivity to 5-HT and U-46619 but not methacholine or histamine. When the U-46619 dose-response curve was constructed following treatment of the animals with atropine (1 mgikg. intravenously), airway hyperresponsiveness was no longer significant. As an index of airway inflammation, lung weights were significantly heavier in ovalbumin-challenged animals, than in saline-challenged controls. The results of this study with intravenously administered spasmogens does not support claims that ovalbumininduced airway hyperreactivity in the guinea-pig is a 'non-specific' phenomenon.

Airway reactivity, inflammatory cell influx and nitric oxide in guinea‐pig airways after lipopolysaccharide inhalation

“…These respective neutrophilic and eosinophilic inflammatory diseases are also associated with an elevated pulmonary production of NO, measured in exhaled air and as NO metabolites in BAL fluid ( Kanazawa et al ., 1998 ). Animal models have been developed to study antigen‐induced airway hyperreactivity ( Sanjar & Morley, 1990 ; Johnson & Broadley, 1999 ). However, there are few in vivo models that simulate AHR associated with a neutrophilic condition, as in COPD.…”

Early and late bronchoconstrictions, airway hyper‐reactivity, leucocyte influx and lung histamine and nitric oxide after inhaled antigen: effects of dexamethasone and rolipram

“…Few studies have demonstrated all of these features simultaneously in the same model, Danahay and Broadley [21] and Santing et al [22] having shown them in the conscious guinea‐pig. Most investigators have utilized anaesthetized animal models to examine airway function [20, 23, 24], where the anaesthetic may interfere with vagal tone or sensory reflexes. Others have administered the H 1 ‐histamine receptor antagonist, mepyramine, to protect against fatal anaphylaxis [21, 25], which may alter the effect of histamine on the airways, released from mast cells in response to allergen.…”