Objectives: 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.
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