ADENOSINE-INDUCED BRONCHOCONSTRICTION IN ASTHMA - ROLE OF PARASYMPATHETIC STIMULATION AND ADRENERGIC INHIBITION

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Abstract
Adenosine by inhalation causes bronchoconstriction in asthmatic but not in normal subjects by an undefined mechanism. The roles of cholinergic reflex stimulation and decreased .beta.2-adrenoceptor responsiveness were investigated to explain adenosine''s bronchoconstrictor action. The protection afforded by the inhaled muscarinic cholinergic antagonist, ipratropium bromide (IB) 1 mg, from bronchoconstriction induced by inhaled adenosine was compared with that of methacholine in 8 allergic asthmatic subjects. After saline placebo, the geometric mean concentrations of adenosine required to produce a 20% fall in FEV [forced expiratory volume 1 s], (PCf20 [provocation concentration causing a 15% fall in FEV1]) was 2.20 mg/ml and a 35% fall in SGaw [specific airway conductance] (PCS35 [provocation concentration causing a 35% fall in SGaw]) was 1.97 mg/ml, which compared to 0.13 and 0.11 mg/ml, respectively, for methacholine. The IB increased FEV1 by 11-15% and SGaw by 69-73% and provided a large degree of protection against methacholine, with a geometric mean concentration ratio (CR) of 196 when airway caliber was measured as SGaw (P < 0.001). IB provided little protection against adenosine-induced bronchoconstriction (CR 1.3 for SGaw and 1.51 for FEV1). .beta.2-Adrenoceptor responsiveness of the airways after inhaled adenosine and histamine was further studied in 12 asthmatic subjects by observing the antibronchoconstrictor effect of inhaled isoproterenol. After equivalent degrees of bronchoconstrictor, 35-36% fall in FEV1 and 60-62% fall in SGaw cumulative doses of inhaled isoproterenol produced almost identical maximal increases in FEV1 and SGaw after adenosine as achieved after histamine. The geometric mean isoproterenol doses required to produce 50% maximal bronchodilation (ID50) were 11 .mu.g for FEV1 and 9 .mu.g for SGaw after adenosine and 5 .mu.g for FEV1 and 11 .mu.g for SGaw after histamine (NS). Bronchoconstriction induced by adenosine is not mediated by stimulation of cholinergic reflexes or by decreased .beta.2-adrenoceptor responsiveness of the airways.