Impaired alveolar liquid clearance after 48-h isoproterenol infusion spontaneously recovers by 96 h of continuous infusion

Abstract

We previously demonstrated that 48-h isoproterenol (Iso) infusion in rats impaired the ability of β-adrenoceptor (β-AR) agonists to increase alveolar liquid clearance (ALC). In this study, we determined whether this impairment persisted over longer time periods by infusing 400 μg·kg−1·h−1 Iso by osmotic minipump for 24–144 h ( n = 6–7/group). ALC in control rats was 19.0 ± 2.4 (SD)% of instilled volume absorbed per hour. In Iso-infused rats, ALC was elevated at 24 h (34.9 ± 2.4%) and decreased at 48 h (15.2 ± 4.4%) and had recovered to 24 h values at 96 h (37.3 ± 3.8%) and 144 h (35.2 ± 3.3%). Plasma Iso concentrations remained elevated at all Iso infusion times. Peripheral lung β2-AR expression exhibited a parallel time course, with a reduction in expression observed at 48 h, followed by an increase to 24 h values at 96 and 144 h. Propranolol prevented the increase in ALC observed at 96 and 144 h, indicating that the recovery in ALC was mediated by a recovery of β-AR function and β-AR signaling. ALC at 96 and 144 h could not be further increased by terbutaline, indicating that ALC was maximally stimulated. These data indicate that recovery of β-AR-stimulated ALC can occur in the continued presence of Iso and is mediated by a recovery of the ability of the distal lung epithelium to respond to β-AR stimulation.