Pharmacological Studies on Active Bronchial Anaphylaxis in the Rat

Abstract

Pharmacologic studies upon the active bronchial anaphylactic response considered to be mediated primarily by reagin-type antibodies were carried out in rats. Inhibition of the response by pharmacologic-mediator antagonists at maximally active doses were methysergide > mepyramine = atropine, but burimamide, indomethacin, mecamylamine, and bilateral vagotomy were ineffective. This suggests that 5-hydroxytryptamine is the major pharmacologic mediator involved in the response, histamine acting upon H₁ receptors is contributory, involvement of prostaglandins and vagal reflexes are minor, and atropine probably exerts a moderate direct bronchial smooth-muscle relaxant effect. Activation of β-adrenergic receptors with isoproterenol is also inhibitory whereas sub-maximal bronchoconstrictor responses are enhanced by β-adrenergic blockade with propranolol. A dose-related bell-shaped inhibition was observed after disodium cromoglycate and dexamethasone was active only with pretreatment over a 3-day period. However, ineffective doses of either disodium cromoglycate or dexamethasone given alone become markedly effective when combined, indicating marked synergistic drug action. The data suggest that the active bronchial anaphylactic rat used in the present study provides an animal model similar to that of the immediate (type I) reagin-mediated asthmatic reactions in man. This model could therefore provide a greater index of predictability for clinical drug utility in human asthma than exists at present.