title: Aldosterone augments Na+-induced reduction of cardiac norepinephrine reuptake.
abstract: Impairment of the cardiac norepinephrine (NE) reuptake by the neuronal NE transporter contributes to enhanced cardiac NE net release in congestive heart failure. Elevated plasma levels of aldosterone (AL) promote sympathetic overstimulation in failing hearts by unclear mechanisms. Our aim was to evaluate if elevated AL and/or alterations in Na(+) intake regulate cardiac NE reuptake. To test the effects of AL and Na(+) on cardiac NE reuptake, Wistar rats were fed a normal-salt (NS) diet (0.2% NaCl), a low-salt (LS) diet (0.015% NaCl), or a high-salt (HS) diet (8% NaCl). Another group of animals received AL infusion alone (0.75 μg/h) or AL infusion plus HS diet. Specific cardiac [(3)H]NE uptake via the NE transporter in a Langendorff preparation and AL plasma levels were measured at different time points between 5 and 42 days of treatment. To compare these findings from healthy animals with a disease model, Dahl salt-sensitive rats were investigated as a model of congestive heart failure with endogenously elevated AL. In summary, neither exogenous nor endogenous elevations of AL alone were sufficient to reduce cardiac NE reuptake. Only the HS diet induced a reduction of NE reuptake by 26%; additional infusion of AL augmented this effect to a further reduction of NE reuptake by 36%. In concordance, Dahl salt-sensitive rats treated with a HS diet displayed elevated AL and a marked reduction of NE reuptake. We conclude that exogenous or endogenous AL elevations alone do not reduce cardiac NE reuptake, but AL serves as an additional factor that negatively regulates cardiac NE reuptake in concert with HS intake.
authors.affiliation: Department of Cardiology, University of Heidelberg, Heidelberg, Germany; German Centre for Cardiovascular Research, Heidelberg/Mannheim, Germany; michael.kreusser@med.uni-heidelberg.de.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Kreusser
authors.affiliation: Department of Cardiology, University of Heidelberg, Heidelberg, Germany; German Centre for Cardiovascular Research, Heidelberg/Mannheim, Germany;
authors.forename: Lorenz H
authors.initials: LH
authors.lastname: Lehmann
authors.affiliation: Department of Cardiology, University of Heidelberg, Heidelberg, Germany; German Centre for Cardiovascular Research, Heidelberg/Mannheim, Germany;
authors.forename: Johannes H
authors.initials: JH
authors.lastname: Riffel
authors.affiliation: Department of Cardiology, Theresienkrankenhaus, Mannheim, Germany; and.
authors.forename: Markus
authors.initials: M
authors.lastname: Haass
authors.affiliation: Department of Pharmacology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Maser-Gluth
authors.affiliation: Department of Cardiology, University of Heidelberg, Heidelberg, Germany; German Centre for Cardiovascular Research, Heidelberg/Mannheim, Germany;
authors.forename: Johannes
authors.initials: J
authors.lastname: Backs
authors.affiliation: Department of Cardiology, University of Heidelberg, Heidelberg, Germany; German Centre for Cardiovascular Research, Heidelberg/Mannheim, Germany;
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Katus
authors.affiliation: Department of Cardiology, University of Heidelberg, Heidelberg, Germany; German Centre for Cardiovascular Research, Heidelberg/Mannheim, Germany;
authors.forename: Sebastian J
authors.initials: SJ
authors.lastname: Buss
mesh_terms: D000450:Aldosterone / Q000097:blood*; D000818:Animals; D001692:Biological Transport; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020303:Rats, Inbred Dahl; D017208:Rats, Wistar; D017673:Sodium Chloride, Dietary / Q000009:adverse effects / Q000378:metabolism*
chemical_list: D050484:Norepinephrine Plasma Membrane Transport Proteins; D017673:Sodium Chloride, Dietary; D000450:Aldosterone; D009638:Norepinephrine
keywords: Dahl rats; aldosterone; congestive heart failure; norepinephrine; sodium