Circadian variation in adrenergic responses in asthmatic subjects

1. To determine whether circadian variations in adrenergic responsiveness might underlie nocturnal wheezing in asthma, we measured cardiovascular, airway and plasma adenosine 3':5'-cyclic monophosphate (cyclic AMP) responses to stepwise infusions of L-adrenaline (0.01, 0.03 and 0.075 microgram min-1 kg-1) at 4 h intervals over 24 h in five extrinsic asthmatic men. 2. Peak expiratory flow, blood pressure, heart rate and plasma cyclic AMP showed a significant circadian variation with peak values at 16.00 hours and trough values at 04.00 hours. 3. The beta 2-adrenoceptor-mediated increases in peak flow and cyclic AMP were similar at all times, but adrenergic responsiveness (measured by response/log dose of infused adrenaline) was greater at 04.00 hours than at 16.00 hours because of the lower baseline values at night. 4. Blood pressure and heart rate responses to adrenaline infusions did not significantly differ over 24 h. 5. Airway responses to inhaled adrenaline were studied on the second day; the mean peak flow after adrenaline was similar at 16.00 hours to that at 04.00 hours and since the pretreatment values were lower at 04.00 hours, the magnitude of response to inhaled adrenaline was greater at night. 6. We conclude that there is no significant circadian change in adrenergic responses in asthma and that adrenoreceptor dysfunction is not important in the pathogenesis of nocturnal asthma.