Norepinephrine Increases Alveolar Fluid Reabsorption and Na,K-ATPase Activity

• Published in: American journal of respiratory and critical care medicine 2004-10, Vol.170 (7), p.730-736
• Main Authors: Azzam, Zaher S, Adir, Yochai, Crespo, Astrid, Comellas, Alejandro, Lecuona, Emilia, Dada, Laura A, Krivoy, Norberto, Rutschman, David H, Sznajder, Jacob I, Ridge, Karen M
• Format: Article
• Language: English
• Subjects: Adrenergic alpha-Agonists - adverse effects; Adrenergic alpha-Agonists - therapeutic use; Adrenergic alpha-Antagonists - pharmacology; Adrenergic alpha-Antagonists - therapeutic use; Adrenergic beta-Antagonists - pharmacology; Adrenergic beta-Antagonists - therapeutic use; Adrenergic receptors; Amiloride - pharmacology; Amiloride - therapeutic use; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Biological and medical sciences; Biological Transport - drug effects; Clonidine - pharmacology; Clonidine - therapeutic use; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Edema; Enzymes; Intensive care medicine; Lungs; Male; Medical sciences; Norepinephrine - adverse effects; Norepinephrine - therapeutic use; Octopamine - pharmacology; Octopamine - therapeutic use; Ouabain - pharmacology; Ouabain - therapeutic use; Pathogens; Phenylephrine - pharmacology; Phenylephrine - therapeutic use; Polymerase chain reaction; Prazosin - pharmacology; Prazosin - therapeutic use; Propranolol - pharmacology; Propranolol - therapeutic use; Pulmonary Alveoli - drug effects; Pulmonary Edema - chemically induced; Pulmonary Edema - metabolism; Pulmonary Edema - prevention & control; Rats; Rats, Sprague-Dawley; Sodium-Potassium-Exchanging ATPase - antagonists & inhibitors; Sodium-Potassium-Exchanging ATPase - drug effects; Up-Regulation - drug effects; Water-Electrolyte Balance - drug effects; Water-Electrolyte Balance - physiology; Yohimbine - pharmacology; Yohimbine - therapeutic use
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.200308-1127OC

The purpose of this study was to determine whether alpha-adrenergic receptor agonists have a role in alveolar fluid reabsorption, via Na,K-ATPase, in the alveolar epithelium. Alveolar fluid reabsorption increased approximately twofold with increasing concentrations of norepinephrine (NE) as compared with control rats. Treatment with the nonselective alpha-adrenergic receptor agonist, octopamine, and the specific alpha(1) agonist, phenylephrine, increased alveolar fluid reabsorption by 54 and 40%, respectively, as compared with control. The specific alpha(1)-adrenergic receptor antagonist, prazosin, inhibited the stimulatory effects of NE by approximately 30%, whereas alpha(2)-adrenergic antagonist, yohimbine, did not prevent the stimulatory effects of NE. The administration of ouabain, Na,K-ATPase inhibitor, prevented the NE-mediated increase in alveolar fluid reabsorption. In parallel with these changes, NE increased Na,K-ATPase activity and protein abundance in alveolar epithelial type II cells via the alpha(1)- and beta-adrenergic receptor. We report here that NE increased alveolar fluid reabsorption via the activation of both alpha(1)- and beta-adrenergic receptors, but not alpha(2)-adrenergic receptors. These effects are due to increased activity and abundance of the Na,K-ATPase in the basolateral membrane of ATII cells.