Normal aging impairs upregulation of the beta-adrenergic but not the alpha-adrenergic response: Aging and adrenergic upregulation

Objectives: To determine if centrally reducing sympathetic tone with clonidine will reverse the downregulation in the alpha-adrenergic (alpha AR) and beta-adrenergic (PAR) responses seen with normal aging. Methods: Twelve rigorously screened young adult (mean age, 26 years) and 15 older adult (mean age, 69 years) subjects were studied before and after using the clonidine patch (TTS-2) for 2 weeks. PAR (isoproterenol at 35 ng/kg/min) and aAR (phenylephrine at 1.0 mu g/kg/min) were assessed using radionuclide measures of end diastolic, end systolic, and stroke volume indices, cardiac index, and ejection fraction. Results: Clonidine reduced resting plasma norepinephrine and this reduction was greater in older subjects (-47 +/- 3 versus -26 +/- 6%, P = 0.001). After 2 weeks of clonidine patch, upregulation of the PAR was significantly higher in young subjects for heart rate (+10.7 +/- 1.5 versus +4.6 +/- 1.5 bpm; P = 0.01). There was no significant age-associated difference in the upregulation of the alpha AR with clonidine for systolic, diastolic, and mean blood pressure or systemic vascular resistance. Conclusions: With aging, there is an impaired resensitization of the chronotropic PAR response with central sympathetic downregulation that is not seen with the alpha AR.