Propranolol-induced airway hyperreactivity in guinea-pigs.

Abstract

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.

• Authors: U M Ney
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 79 Issue 4 Pg. 1003-9 (Aug 1983) ISSN: 0007-1188 [Print] England
• PMID: 6140046 (Publication Type: Journal Article)

Chemical References

• Adrenergic beta-Antagonists
• Chromones
• Pyrazoles
• Serotonin
• 4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine
• FPL 55712
• Propranolol
• Practolol

Topics

• 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