Clinical study: cardiac arrhythmias
Age-dependent changes of cardiac neuronal noradrenaline reuptake transporter (uptake1) in the human heart

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Abstract

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 μmol/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 μmol/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.

Abbreviations

RA
right atrium/atria/atrial
NAT
neuronal noradrenaline transporter
NYHA
New York Heart Association

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This work was supported by a grant (SFB 598-02 to Dr. Brodde) of the Deutsche Forschungsgemeinschaft, Bonn, Germany.