Enhanced alveolar fluid clearance following 72 h of continuous isoproterenol infusion in rats.
OBJECTIVE
We wished to determine the effect of continuous β-receptor stimulation on alveolar fluid clearance and to elucidate the mechanisms behind this effect.


METHODS
Alveolar fluid clearance was measured in anaesthetized rats pretreated for 72 h with the β-agonist isoproterenol (200 μg kg(-1) h(-1)  sc) or vehicle. Alveolar fluid clearance in artificially ventilated rats was determined over 1 h by infusion of isotonic Ringer solution containing (125) I-albumin into the lungs. Additionally, alveolar fluid clearance was determined when amiloride or l-cis-diltiazem was added to the solution to block ENaC and cyclic nucleotide-gated (CNG) channels respectively.


RESULTS
Isoproterenol treatment induced a 42% increase in alveolar fluid clearance (18.9 ± 1.4%) vs. vehicle (13.3 ± 3.3%). Addition of amiloride resulted in a net decrease of 8% in both groups, while l-cis-diltiazem caused a net decrease of 12% in isoproterenol-treated animals, but only 5% in vehicle-treated animals. Western blotting showed that isoproterenol treatment increased the abundance of the α-ENaC and β-ENaC subunits (223 ± 51% and 274 ± 55% of vehicle, respectively) but we saw no changes in protein level of the γ-EnaC subunit.


CONCLUSIONS
Continuous β-adrenoceptor stimulation with isoproterenol enhances alveolar fluid clearance through alternative pathways involving l-cis-diltiazem-sensitive channels.
Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
L R E
LR
Pedersen
K M
KM
Müllertz
O
O
Amtorp
S
S
Christensen
T E N
TE
Jonassen
D000318:Adrenergic beta-Agonists / Q000008:administration & dosage*; D000418:Albumins / Q000378:metabolism; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D004110:Diltiazem / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D053503:Epithelial Sodium Channels / Q000187:drug effects / Q000378:metabolism; D015918:Infusion Pumps, Implantable; D055104:Infusions, Subcutaneous; D007545:Isoproterenol / Q000008:administration & dosage*; D008297:Male; D010539:Permeability; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012121:Respiration, Artificial; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013997:Time Factors
D000318:Adrenergic beta-Agonists; D000418:Albumins; D054815:Cyclic Nucleotide-Gated Cation Channels; D053503:Epithelial Sodium Channels; D026941:Sodium Channel Blockers; D000584:Amiloride; D004110:Diltiazem; D007545:Isoproterenol