EXACERBATION OF AIRWAY HYPERREACTIVITY BY (PLUS-OR-MINUS)SALBUTAMOL IN SENSITIZED GUINEA-PIGS

In guinea pigs passively sensitized to ovalbumin, sustained (6 days) subcutaneous infusion of (+/-)salbutamol (1 mg/kg/day) induced significant airway obstruction and heightened responsivity to airway spasmogens. Of these animals, a substantial proportion (78/235) were too responsive to injected spasmogens to permit infusion of ovalbumin or died following infusion of ovalbumin; yet there were few deaths (2/166) amongst the sensitized animals not exposed to (+/-)salbutamol. In comparison to the animals not exposed to (+/-)salbutamol, infusion of ovalbumin led to exaggerated responsivity of the airways to leukotriene C4, leukotriene E4, histamine, serotonin and acetylcholine, but not to prostaglandin F2alpha or bradykinin. The capacity of sustained exposure to high doses of (+/-)salbutamol to induce airway hyperreactivity to allergic mediators may account for an association between asthma death and regular, excessive use of sympathomimetics.