Propranolol‐induced airway hyperreactivity in guinea‐pigs

• Published in: British journal of pharmacology Vol. 79; no. 4; pp. 1003 - 1009
• Main Author: Ney, U.M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.08.1983; Nature Publishing Group
• Subjects: 4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; Adrenergic beta-Antagonists - pharmacology; Airway Resistance - drug effects; Animals; Bronchi - drug effects; Chromones - pharmacology; Female; Guinea Pigs; Male; Practolol - pharmacology; Propranolol - therapeutic use; Pyrazoles - pharmacology; Serotonin - pharmacology; Stereoisomerism
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1983.tb10548.x

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.