Propranolol-induced airway hyperreactivity in guinea-pigs.
In anaesthetized, spontaneously breathing guinea-pigs, enhanced bronchoconstrictor responses (increases RL) to histamine were measured following intravenous injection of practolol, (+/-)-propranolol, (+)- and (-)-propranolol. Propranolol enhanced not only histamine- but 5-hydroxytryptamine (5-HT)-induced bronchoconstrictions and its effects lasted up to 2 h. This increased airway sensitivity was not due to beta-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 beta-adrenoceptor blockade in the airways. The enhanced histamine- and 5-HT-induced bronchoconstrictions were antagonized by the leukotriene antagonist FPL 55712 and by the lipoxygenase/cyclo-oxygenase inhibitor BW755c. The results demonstrate that endogenously released leukotrienes can produce not only a direct bronchospasm but may enhance the effects of other bronchoconstrictor agents. The relevance of this leukotriene-mediated hyperreactivity to the non-specific airway hyperreactivity seen in asthmatics is discussed.
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000403:Airway Resistance / Q000187:drug effects*; D000818:Animals; D001980:Bronchi / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D008297:Male; D011217:Practolol / Q000494:pharmacology; D011433:Propranolol / Q000627:therapeutic use*; D011720:Pyrazoles / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D013237:Stereoisomerism
D000319:Adrenergic beta-Antagonists; D002867:Chromones; D011720:Pyrazoles; D012701:Serotonin; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; C006312:FPL 55712; D011433:Propranolol; D011217:Practolol