β2‐Adrenoceptor blockade is the basis of guinea‐pig bronchial hyper‐responsiveness to leukotriene C4 and other agonists

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Abstract
1 Four β-adrenoceptor antagonists, namely (−)-propranolol, (+)-propranolol, ICI-118551 and (±)-practolol, were investigated for their effects on leukotriene C4 (LTC4)-induced bronchoconstriction in the anaesthetized guinea-pig. (−)-Propranolol was also investigated for its effects on acetylcholine and histamine bronchospasm in the anaesthetized guinea-pig, and on LTC4-induced contractions of guinea-pig isolated trachea and lung parenchyma. 2 The various β-adrenoceptor antagonists potentiated, dose-dependently, the bronchoconstriction induced by threshold doses of LTC4 and the intensity of the potentiation correlated with the β2-blocking capacity possessed by the drugs. 3 (−)-Propranolol potentiated the bronchospasm induced by threshold doses of acetylcholine and histamine but to a lesser degree than the LTC4-induced bronchospasm. 4 The airway hyper-responsiveness induced by (−)-propranolol was unaffected by pretreatment with mepyramine, cyproheptadine, phenoxybenzamine, atropine or indomethacin. 5 The airway hyper-responsiveness induced by (−)-propranolol persisted even in adrenalectomized or reserpine-treated guinea-pigs, although adrenalectomy induced some increase in airway responsiveness. 6 (−)-Propranolol had no effect on LTC4, histamine and acetylcholine-induced contractions of isolated trachea and lung parenchyma. 7 The results show that the airway hyper-responsiveness induced by β-adrenoceptor antagonists generally correlates with their β2-blocking activity. The possibility remains that some other unknown mechanism(s) may also be implicated.