Prolonged isoproterenol infusion impairs the ability of beta(2)-agonists to increase alveolar liquid clearance.
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.
Morgan
Eric E
EE
Department of Physiology, Northeastern Ohio Universities College of Medicine, 4209 State Rte. 44, Rootstown, OH 44272-0095, USA.
Hodnichak
Cheryl M
CM
Stader
Sonya M
SM
Maender
Kay C
KC
Boja
John W
JW
Folkesson
Hans G
HG
Maron
Michael B
MB
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D015536:Down-Regulation / Q000187:drug effects; D004347:Drug Interactions; D004847:Epithelial Cells / Q000378:metabolism; D015633:Extravascular Lung Water / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism*; D011652:Pulmonary Circulation / Q000502:physiology; D011654:Pulmonary Edema / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism*; D013726:Terbutaline / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D007545:Isoproterenol; D013726:Terbutaline