1. Airway, metabolic and cyclic nucleotide responses to intravenous salbutamol were measured in five patients with mild asthma who had taken no medication in the week before the study. The studies were repeated after the patient had taken regular inhaled salbutamol for 4 weeks, in doses increasing to 2000 μg daily in week 4.
2. The pretreatment airway, metabolic and cyclic nucleotide responses to salbutamol were similar to those previously reported in normal subjects. These patients therefore did not show evidence of partial β-adrenoceptor blockade.
3. After 4 weeks' salbutamol therapy the airway response to intravenous salbutamol was unchanged.
4. The glucose, pyruvate and adenosine 3′:5′-cyclic monophosphate (cyclic AMP) responses to intravenous salbutamol were depressed after regular salbutamol administration. The dose-response curve for non-esterified fatty acids and insulin, though displaced downwards, did not indicate an impaired response to salbutamol since the shape was unchanged. There was no significant change in the lactate, glycerol and total ketone response.
5. This study confirms that tissues differ in the ease with which they develop resistance to β-adrenoceptor agonists. Asthmatic airways appear to be relatively protected from developing resistance when compared with other tissues in asthmatic patients and when compared with the airways of normal subjects.