title: Beta-adrenoceptor stimulation of alveolar fluid clearance is increased in rats with heart failure.
abstract: The alveolar epithelium plays a critical role in resolving pulmonary edema. We thus hypothesized that its function might be upregulated in rats with heart failure, a condition that severely challenges the lung's ability to maintain fluid balance. Heart failure was induced by left coronary artery ligation. Echocardiographic and cardiovascular hemodynamics confirmed its development at 16 wk postligation. At that time, alveolar fluid clearance was measured by an increase in protein concentration over 1 h of a 5% albumin solution instilled into the lungs. Baseline alveolar fluid clearance was similar in heart failure and age-matched control rats. Terbutaline was added to the instillate to determine whether heart failure rats responded to beta-adrenoceptor stimulation. Alveolar fluid clearance in heart failure rats was increased by 194% after terbutaline stimulation compared with a 153% increase by terbutaline in control rats. To determine the mechanisms responsible for this accelerated alveolar fluid clearance, we measured ion transporter expression (ENaC, Na-K- ATPase, CFTR). No significant upregulation was observed for these ion transporters in the heart failure rats. Lung morphology showed significant alveolar epithelial type II cell hyperplasia in heart failure rats. Thus, alveolar epithelial type II cell hyperplasia is the likely explanation for the increased terbutaline-stimulated alveolar fluid clearance in heart failure rats. These data provide evidence for previously unrecognized mechanisms that can protect against or hasten resolution of alveolar edema in heart failure.
authors: Department of Integrative Medical Sciences, Northeastern Ohio Universities Colleges of Medicine and Pharmacy, 4209 State Route 44, PO Box 95, Rootstown, OH 44272-0095, USA.
authors: Michael B
authors: MB
authors: Maron
authors: Daniel J
authors: DJ
authors: Luther
authors: Charles F
authors: CF
authors: Pilati
authors: Vahagn
authors: V
authors: Ohanyan
authors: Tianbo
authors: T
authors: Li
authors: Shyny
authors: S
authors: Koshy
authors: Walter I
authors: WI
authors: Horne
authors: J Gary
authors: JG
authors: Meszaros
authors: Jon M
authors: JM
authors: Walro
authors: Hans G
authors: HG
authors: Folkesson
mesh_terms: D000818:Animals; D001826:Body Fluids / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006333:Heart Failure / Q000097:blood / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology*; D006728:Hormones / Q000097:blood; D006965:Hyperplasia; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000097:blood / Q000000981:diagnostic imaging / Q000473:pathology; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013726:Terbutaline / Q000494:pharmacology; D014463:Ultrasonography
chemical_list: D006728:Hormones; D007473:Ion Channels; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D013726:Terbutaline