Prolonged isoproterenol infusion impairs the ability of beta(2)-agonists to increase alveolar liquid clearance.

Prolonged isoproterenol infusion impairs the ability of beta(2)-agonists to increase alveolar liquid clearance.

Morgan Eric E; Hodnichak Cheryl M; Stader Sonya M; Maender Kay C; Boja John W; Folkesson Hans G; Maron Michael B

American journal of physiology. Lung cellular and molecular physiology

2002

2002-04

We determined if prolonged isoproterenol (Iso) infusion in rats impaired the ability of the beta(2)-adrenergic agonist terbutaline to increase alveolar liquid clearance (ALC). We infused rats with Iso (at rates of 4, 40, or 400 microg.kg(-1).h(-1)) or vehicle (0.001 N HCl) for 48 h using subcutaneously implanted miniosmotic pumps. After this time, the rats were anesthetized, and ALC was determined (by mass-balance after instillation of Ringer lactate containing albumin into the lungs) under baseline conditions and after terbutaline administration. Baseline and terbutaline-stimulated ALC in vehicle-infused rats averaged, respectively, 19.6 +/- 1.2% (SE) and 44.7 +/- 1.5%/h. The ability of terbutaline to increase ALC was eliminated at 400 microg.kg(-1).h(-1)Iso, inhibited by 26% at 40 microg.kg(-1).h(-1) Iso, and was not affected by 4 microg.kg(-1).h(-1) Iso. beta-adrenergic receptor (betaAR) density of freshly isolated alveolar epithelial type II (ATII) cells from Iso-infused rats was reduced by the 40 and 400 microg.kg(-1).h(-1) infusion rates. These data demonstrate that prolonged exposure to beta-agonists can impair the ability of beta(2)-agonists to stimulate ALC and produce ATII cell betaAR downregulation.

Adrenergic; Adrenergic beta-Agonists/*pharmacology; Animals; beta/metabolism; Down-Regulation/drug effects; Drug Interactions; Epithelial Cells/metabolism; Extravascular Lung Water/*metabolism; Isoproterenol/*pharmacology; Male; Pulmonary Alveoli/cytology/*metabolism; Pulmonary Circulation/physiology; Pulmonary Edema/metabolism; Rats; Receptors; Respiratory Mucosa/cytology/*metabolism; Sprague-Dawley; Terbutaline/pharmacology

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