Submitted on January 17, 2006
Accepted on February 14, 2006
Impaired alveolar liquid clearance after 48 h isoproterenol infusion spontaneously recovers by 96 h of continuous infusion
Michael B Maron1*, Hans G Folkesson1, Sonya M Stader1, and Cheryl M Hodnichak1
1 Department of Physiology and Pharmacology, Northeastern Ohio Universities College of Medicine, Rootstown, OH, USA
* To whom correspondence should be addressed. E-mail: mbm{at}neoucom.edu.
We previously demonstrated that 48 h isoproterenol (Iso) infusion in rats impaired the ability of 
-adrenoceptor (AR) agonists to increase alveolar liquid clearance (ALC). In this study, we determined if this impairment persisted over longer time periods by infusing 400 µg/kg/h Iso by mini-osmotic pump for 24-144 h (n=6-7/group). ALC in control rats was 19.0 ± 2.4 (SD)% of instilled volume absorbed/h. In Iso-infused rats, ALC was elevated at 24 h (34.9 ± 2.4%), decreased at 48 h (15.2 ± 4.4%), and had recovered to 24 h values at 96 (37.3 ± 3.8%) and 144 h (35.2 ± 3.3%). Plasma Iso concentrations remained elevated at all Iso infusion times. Peripheral lung 2AR 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 AR function and 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 AR-stimulated ALC can occur in the continued presence of Iso and was mediated by a recovery of the ability of the distal lung epithelium to respond to AR stimulation.
