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Mechanisms of ozone-induced bronchial hyperreactivity to muscarinic agonists in the guinea pig

Thesis/Dissertation ·
OSTI ID:6608640

Bronchial hyperreactivity, a chief characteristic of asthma, is poorly understood mechanistically. Its development in ozone-exposed guinea pigs was studied in this dissertation research. Reactivity was assessed in awake, spontaneously breathing animals by measuring specific airway resistance (SRaw) as a function of increasing muscarinic bronchoconstrictor challenge. In the first study, improvements in the reactivity measurement were seen by using (1) propranolol pretreatment (10 mg/kg IP, 1/2 hr before measurement) and (2) intravenous (rather than aerosolized) muscarinic challenge. Both (1) decreased its population wide variation and (2) increased its intra-animal reproducibility. Secondly, characteristics of ozone-induced bronchial hyperreactivity, such as (1) its airway mucosal permeability dependence, (2) its time course of development, and (3) its ozone-dose dependence were studied. The relationship between airway mucosa neutrophilic infiltration and the development of this hyperreactivity was examined in the third and fourth study. In the third, a time course study showed that development of hyperreactivity occurred before the neutrophilic infiltration phase, and correlated best with a decrease in identifiable mucosal goblet cells and increase in identifiable mucosoal mast cells. In the fourth, the development of ozone-induced hyperreactivity in animals made granulocytopenic with cyclophosphamide and cortisone acetate treatment was studied. In the final study, the effects of indomethacin on the development of this hyperreactivity was assessed.

Research Organization:
California Univ., Irvine (USA)
OSTI ID:
6608640
Country of Publication:
United States
Language:
English