Propranolol-induced airway hyperreactivity in guinea-pigs

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Abstract
1 In anaesthetized, spontaneously breathing guinea-pigs, enhanced bronchoconstrictor responses (↑ RL) to histamine were measured following intravenous injection of practolol, (±)-propranolol, (+)- and (−)-propranolol. 2 Propranolol enhanced not only histamine- but 5-hydroxytryptamine (5-HT)-induced bronchoconstrictions and its effects lasted up to 2 h. 3 This increased airway sensitivity was not due to β-adrenoceptor blockade because: (a) similar effects were produced by racemic propranolol and its two isomers (+)- and (−)-propranolol and (b) whilst equal doses of (±)- and (+)-propranolol produced the same potentiation of histamine bronchoconstriction, only (±)-propranolol also caused a measurable β-adrenoceptor blockade in the airways. 4 The enhanced histamine- and 5-HT-induced bronchoconstrictions were antagonized by the leukotriene antagonist FPL 55712 and by the lipoxygenase/cyclo-oxygenase inhibitor BW755c. 5 The results demonstrate that endogenously released leukotrienes can produce not only a direct bronchospasm but may enhance the effects of other bronchoconstrictor agents. 6 The relevance of this leukotriene-mediated hyperreactivity to the non-specific airway hyperreactivity seen in asthmatics is discussed.