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

Abstract

We wished to determine the effect of continuous β-receptor stimulation on alveolar fluid clearance and to elucidate the mechanisms behind this effect. Alveolar fluid clearance was measured in anaesthetized rats pretreated for 72h with the β-agonist isoproterenol (200μgkg(-1) h(-1) sc) or vehicle. Alveolar fluid clearance in artificially ventilated rats was determined over 1h 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. 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. Continuous β-adrenoceptor stimulation with isoproterenol enhances alveolar fluid clearance through alternative pathways involving l-cis-diltiazem-sensitive channels.