METAPROTERENOL RESPONSIVENESS AFTER METHACHOLINE-INDUCED AND HISTAMINE-INDUCED BRONCHOCONSTRICTION

We investigated whether the bronchodilator response to a beta-adrenerg ic agonist is influenced by the mechanism of induced bronchoconstricti on. Normal subjects and asymptomatic asthmatics inhaled a dry aerosol (mass median aerodynamic diameter 1.5 mu m) with increasing concentrat ions of methacholine or histamine to produce a 35% decrease in specifi c airway conductance (SGaw), followed by a single inhalation of a meta proterenol aerosol. By studying normal subjects and asthmatics, we wer e able to compare metaproterenol responsiveness after widely divergent doses of the bronchoprovocative agents but the same degree of broncho constriction. Airway deposition of methacholine, histamine, and metapr oterenol was measured using a quinine fluorescence technique, Mean bas eline SGaw, metaproterenol responsiveness, and metaproterenol mass dep osited were similar in normal subjects and asthmatics. Like,vise, mean SGaw after completion of methacholine and histamine challenge, and th e subsequently deposited metaproterenol mass were similar in the two g roups. After methacholine challenge (mean+/-SD provocative drug mass c ausing a 35% decrease in SGaw, PM(35): 8.94+/-5.96 mu mol in normal su bjects and 0.30+/-0.29 mu mol in asthmatics), metaproterenol increased mean SGaw by 89+/-33% in normal subjects and by 190+/-55% in asthmati cs (p<0.05, two-way analysis of variance), After histamine challenge ( PM(35), 2.92+/-2.49 mu mol in normal subjects and 0.17+/-0.29 mu mol i n asthmatics), metaproterenol increased mean SGaw by 111+/-38% in norm al subjects and 113+/-69% in asthmatics (p=not significant). Thus, for the same degree of bronchoconstriction, metaproterenol responsiveness was influenced by the dose of methacholine but not the dose of histam ine, The differential metaproterenol response could be related to a fu nctional antagonism between muscarinic and beta-adrenergic agonists.