title: Norepinephrine increases alveolar fluid reabsorption and Na,K-ATPase activity.
abstract: 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.
authors.affiliation: Medical Service, Veteran Affairs Chicago Health Care System, Illinois, USA.
authors.forename: Zaher S
authors.initials: ZS
authors.lastname: Azzam
authors.forename: Yochai
authors.initials: Y
authors.lastname: Adir
authors.forename: Astrid
authors.initials: A
authors.lastname: Crespo
authors.forename: Alejandro
authors.initials: A
authors.lastname: Comellas
authors.forename: Emilia
authors.initials: E
authors.lastname: Lecuona
authors.forename: Laura A
authors.initials: LA
authors.lastname: Dada
authors.forename: Norberto
authors.initials: N
authors.lastname: Krivoy
authors.forename: David H
authors.initials: DH
authors.lastname: Rutschman
authors.forename: Jacob I
authors.initials: JI
authors.lastname: Sznajder
authors.forename: Karen M
authors.initials: KM
authors.lastname: Ridge
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000009:adverse effects* / Q000627:therapeutic use; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D000584:Amiloride / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D008297:Male; D009638:Norepinephrine / Q000009:adverse effects* / Q000627:therapeutic use; D009655:Octopamine / Q000494:pharmacology / Q000627:therapeutic use; D010042:Ouabain / Q000494:pharmacology / Q000627:therapeutic use; D010656:Phenylephrine / Q000494:pharmacology / Q000627:therapeutic use; D011224:Prazosin / Q000494:pharmacology / Q000627:therapeutic use; D011433:Propranolol / Q000494:pharmacology / Q000627:therapeutic use; D011650:Pulmonary Alveoli / Q000187:drug effects*; D011654:Pulmonary Edema / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects; D014882:Water-Electrolyte Balance / Q000187:drug effects / Q000502:physiology; D015016:Yohimbine / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D009655:Octopamine; D010656:Phenylephrine; D015016:Yohimbine; D010042:Ouabain; D000584:Amiloride; D011433:Propranolol; D000254:Sodium-Potassium-Exchanging ATPase; D003000:Clonidine; D009638:Norepinephrine; D011224:Prazosin