Age-dependent changes of cardiac neuronal noradrenaline reuptake transporter (uptake1) in the human heart.

Abstract

The purpose of this study was to elucidate whether the neuronal noradrenaline reuptake transporter (uptake1) undergoes age-dependent regulation in the human heart. Aging is associated with various alterations in cardiovascular function. 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. 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. With increasing age, human myocardial uptake1 activity decreases, possibly because of age-dependent downregulation of uptake1 density.