β2-adrenergic receptor overexpression increases alveolar fluid clearance and responsiveness to endogenous catecholamines in rats

Vidas Dumasius, Jacob I. Sznajder, Zaher S. Azzam, John Boja, Gökhan M. Mutlu, Michael B. Maron, Phillip Factor*

*Corresponding author for this work

Research output: Contribution to journalArticle

90 Scopus citations

Abstract

β-Adrenergic agonists accelerate the clearance of alveolar fluid by increasing the expression and activity of epithelial solute transport proteins such as amiloride-sensitive epithelial Na+ channels (ENaC) and Na,K-ATPases. Here we report that adenoviral-mediated overexpression of a human β2-adrenergic receptor (β2AR) cDNA increases β2AR mRNA, membrane-bound receptor protein expression, and receptor function (procaterol-induced cAMP production) in human lung epithelial cells (A549). Receptor overexpression was associated with increased catecholamine (procaterol)-responsive active Na+ transport and increased abundance of Na,K-ATPases in the basolateral cell membrane. β2AR gene transfer to the alveolar epithelium of normal rats improved membrane-bound β2AR expression and function and increased levels of ENaC (α subunit) abundance and Na,K-ATPases activity in apical and basolateral cell membrane fractions isolated from the peripheral lung, respectively. Alveolar fluid clearance (AFC), an index of active Na+ transport, in β2AR overexpressing rats was up to 100% greater than sham-infected controls and rats infected with an adenovirus that expresses no cDNA. The addition of the β2AR-specific agonist procaterol to β2AR overexpressing lungs did not increase AFC further. AFC in β2AR overexpressing lungs from adrenalectomized or propranolol-treated rats revealed clearance rates that were the same or less than normal, untreated, sham-infected controls. These experiments indicate that alveolar β2AR overexpression improves β2AR function and maximally upregulates β-agonist-responsive active Na+ transport by improving responsiveness to endogenous catecholamines. These studies suggest that upregulation of β2AR function may someday prove useful for the treatment of pulmonary edema.

Original languageEnglish (US)
Pages (from-to)907-914
Number of pages8
JournalCirculation research
Volume89
Issue number10
DOIs
StatePublished - Nov 9 2001

Keywords

  • Adenovirus
  • Alveolar solute transport
  • Gene transfer
  • Pulmonary edema
  • β-adrenergic receptor

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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