Beta 2-adrenoceptor blockade is the basis of guinea-pig bronchial hyper-responsiveness to leukotriene C4 and other agonists.
Four beta-adrenoceptor antagonists, namely (-)-propranolol, (+)-propranolol, ICI-118551 and (+/-)-practolol, were investigated for their effects on leukotriene C4 (LTC4)-induced bronchoconstriction in the anesthetized 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. The various beta-adrenoceptor antagonists potentiated, dose-dependently, the bronchoconstriction induced by threshold doses of LTC4 and the intensity of the potentiation correlated with the beta 2-blocking capacity possessed by the drugs. (-)-Propranolol potentiated the bronchospasm induced by threshold doses of acetylcholine and histamine but to a lesser degree than the LTC4-induced bronchospasm. The airway hyper-responsiveness induced by (-)-propranolol was unaffected by pretreatment with mepyramine, cyproheptadine, phenoxybenzamine, atropine or indomethacin. The airway hyper-responsiveness induced by (-)-propranolol persisted even in adrenalectomized or reserpine-treated guinea-pigs, although adrenalectomy induced some increase in airway responsiveness. (-)-Propranolol had no effect on LTC4, histamine and acetylcholine-induced contractions of isolated trachea and lung parenchyma. The results show that the airway hyper-responsiveness induced by beta-adrenoceptor antagonists generally correlates with their beta 2-blocking activity. The possibility remains that some other unknown mechanism(s) may also be implicated.
D000315:Adrenalectomy; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000403:Airway Resistance / Q000187:drug effects*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001980:Bronchi / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013189:SRS-A / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects; D014590:Uterine Contraction / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D013189:SRS-A; D011433:Propranolol