Enhanced alveolar fluid clearance following 72 h of continuous isoproterenol infusion in rats

• Published in: Acta Physiologica 2012-10, Vol.206 (2), p.142-149
• Main Authors: Pedersen, L. R. E., Müllertz, K. M., Amtorp, O., Christensen, S., Jonassen, T. E. N.
• Format: Article
• Language: English
• Subjects: Adrenergic beta-Agonists - administration & dosage; Albumins - metabolism; alveolar fluid clearance; amiloride; Amiloride - pharmacology; Animals; Biological and medical sciences; Blotting, Western; Cyclic Nucleotide-Gated Cation Channels - antagonists & inhibitors; Cyclic Nucleotide-Gated Cation Channels - metabolism; cyclic nucleotide-gated channels; Diltiazem - pharmacology; Dose-Response Relationship, Drug; epithelial sodium channel; Epithelial Sodium Channels - drug effects; Epithelial Sodium Channels - metabolism; Fundamental and applied biological sciences. Psychology; Infusion Pumps, Implantable; Infusions, Subcutaneous; Isoproterenol - administration & dosage; l-cis-diltiazem; Male; Permeability; Pulmonary Alveoli - drug effects; Pulmonary Alveoli - metabolism; Rats; Rats, Wistar; Respiration, Artificial; Sodium Channel Blockers - pharmacology; Time Factors; Vertebrates: anatomy and physiology, studies on body, several organs or systems; β-agonist
• ISSN: 1748-1708; 1748-1716
• DOI: 10.1111/j.1748-1716.2012.02459.x

Aim 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−1h−1 sc) or vehicle. Alveolar fluid clearance in artificially ventilated rats was determined over 1 h by infusion of isotonic Ringer solution containing 125I‐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. Conclusion Continuous β‐adrenoceptor stimulation with isoproterenol enhances alveolar fluid clearance through alternative pathways involving l‐cis‐diltiazem‐sensitive channels.