Development of "resistance" in beta-adrenergic receptors of asthmatic patients.

Complete in vitro dose-response curves for (see article) -isoproterenol (isoprenaline) sulfate showed no functional defects in bronchial muscular beta-adrenergic receptors in three patients with chronic intrinsic asthma, as compared to 60 patients with normal pulmonary function. Complete in vivo dose-response curves for intravenously infused isoproterenol were obtained in eight outpatients with chronic intrinsic asthma to register effects on bronchial muscle (forced expiratory volume in one second), heart rate, blood pressure, and skeletal muscular tremor. The isoproterenol test was performed before and also during oral treatment with a long-acting selective beta-adrenergic stimulator (terbutaline sulfate, 5 mg three times daily). The study was performed over 12 months to avoid seasonal variation in basal levels of obstruction and was concluded by adding inhaled terbutaline (two inhalations four times daily) to oral therapy. No "resistance" developed in bronchial beta-adrenergic receptors during this prolonged treatment. Inhalation therapy in addition to oral therapy improved bronchodilation without causing resistance. Even six inhalations given four times daily (four- to five-hour intervals) did not cause any bronchial resistance; however, resistance developed in skeletal muscles with decreased tremor and in cardiac beta-adrenergic receptors.