title: Age-dependent changes of cardiac neuronal noradrenaline reuptake transporter (uptake1) in the human heart.
abstract: OBJECTIVE
  The purpose of this study was to elucidate whether the neuronal noradrenaline reuptake transporter (uptake1) undergoes age-dependent regulation in the human heart.
  
  
  BACKGROUND
  Aging is associated with various alterations in cardiovascular function.
  
  
  METHODS
  We determined uptake1 density (by [3H]-nisoxetine binding to membranes) and activity (by accumulation of [3H]-noradrenaline into tissue slices) in the right atria (RA) of 42 patients (age range 3 months to 76 years) undergoing open-heart surgery without apparent heart failure. Moreover, the effects of 1 micromol/l desipramine on the noradrenaline-induced positive inotropic effect were assessed in the isolated, electrically driven RA trabeculae of these patients.
  
  
  RESULTS
  There was a significant negative correlation between RA uptake1 density and age; moreover, RA uptake1 activity was significantly reduced in elderly patients. Desipramine (1 micromol/l) significantly shifted noradrenaline concentration-response curves to the left; this shift was significantly more pronounced in younger patients than in older patients.
  
  
  CONCLUSIONS
  With increasing age, human myocardial uptake1 activity decreases, possibly because of age-dependent downregulation of uptake1 density.
authors.affiliation: Institute of Pharmacology, Martin-Luther-University of Halle-Wittenberg, Halle, Germany.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Leineweber
authors.forename: Thekla
authors.initials: T
authors.lastname: Wangemann
authors.forename: Christine
authors.initials: C
authors.lastname: Giessler
authors.forename: Heike
authors.initials: H
authors.lastname: Bruck
authors.forename: Stefan
authors.initials: S
authors.lastname: Dhein
authors.forename: Martin
authors.initials: M
authors.lastname: Kostelka
authors.forename: Friedrich Wilhelm
authors.initials: FW
authors.lastname: Mohr
authors.forename: Rolf Edgar
authors.initials: RE
authors.lastname: Silber
authors.forename: Otto Erich
authors.initials: OE
authors.lastname: Brodde
mesh_terms: D000293:Adolescent; D018759:Adrenergic Uptake Inhibitors / Q000378:metabolism / Q000494:pharmacology; D000328:Adult; D000367:Age Factors; D000368:Aged; D000375:Aging / Q000502:physiology*; D016275:Atrial Function; D002648:Child; D002675:Child, Preschool; D003891:Desipramine / Q000494:pharmacology; D006325:Heart Atria / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism* / Q000493:pharmacokinetics; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
chemical_list: D018759:Adrenergic Uptake Inhibitors; D011943:Receptors, Adrenergic, beta; D003891:Desipramine; D009638:Norepinephrine