INVESTIGATION OF THE MECHANISM OF PROPRANOLOL-INDUCED BRONCHOCONSTRICTION

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 β‐adrenoceptor blocking drugs, atenolol and practolol. The bronchoconstriction reached a peak in 2 to 4 min and subsided within 15 min. Repeated injections caused identical responses in the airways. The isomer (+)‐propranolol, which has only weak β‐adrenoceptor blocking activity, produced identical responses when given alone or when given after a dose of the racemate, sufficient to cause measurable β‐adrenoceptor blockade in the lungs. After the initial bronchospasm had subsided, the β‐adrenoceptor blocking drugs and the isomer, (+)‐propranolol, produced potentiation of the bronchoconstrictor effects of 5‐hydroxytryptamine and histamine. Both the bronchospasm and the potentiation occurred in adrenal demedullated rats. The results indicate that the bronchoconstrictor effects of these drugs are unrelated to β‐adrenoceptor blockade in the airway smooth muscle. 1979 British Pharmacological Society