Investigation of the mechanism of propranolol-induced bronchoconstriction.

1 Dose-related increases in airways resistance (Raw) and decreases in dynamic lung compliance (Cdyn) were recorded in guinea-pigs and rats following intravenous injection of propranolol and of the cardioselective beta-adrenoceptor blocking drugs, atenolol and practolol. 2 The bronchoconstriction reached a peak in 2 to 4 min and subsided within 15 min. Repeated injections caused identical responses in the airways. 3 The isomer (+)-propranolol, which has only weak beta-adrenoceptor blocking activity, produced identical responses when given alone or when given after a dose of the racemate, sufficient to cause measurable beta-adrenoceptor blockade in the lungs. 4 After the initial bronchospasm had subsided, the beta-adrenoceptor blocking drugs and the isomer, (+)-propranolol, produced potentiation of the bronchoconstrictor effects of 5-hydroxytryptamine and histamine. 5 Both the bronchospasm and the potentiation occurred in adrenal demedullated rats. 6 The results indicate that the bronchoconstrictor effects of these drugs are unrelated to beta-adrenoceptor blockade in the airway smooth muscle.