title: Normal aging impairs upregulation of the beta-adrenergic but not the alpha-adrenergic response: aging and adrenergic upregulation.
abstract: OBJECTIVE
  To determine if centrally reducing sympathetic tone with clonidine will reverse the downregulation in the alpha-adrenergic (alphaAR) and beta-adrenergic (betaAR) 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. betaAR (isoproterenol at 35 ng/kg/min) and alphaAR (phenylephrine at 1.0 microg/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 betaAR 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 alphaAR with clonidine for systolic, diastolic, and mean blood pressure or systemic vascular resistance.
  
  
  CONCLUSIONS
  With aging, there is an impaired resensitization of the chronotropic betaAR response with central sympathetic downregulation that is not seen with the alphaAR.
authors.affiliation: Division of Geriatric Medicine, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada. kmmadden@interchange.ubc.ca
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Madden
authors.forename: Wayne C
authors.initials: WC
authors.lastname: Levy
authors.forename: John R
authors.initials: JR
authors.lastname: Stratton
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology; D005260:Female; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010656:Phenylephrine / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D012727:Sex Characteristics; D015854:Up-Regulation
chemical_list: D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D010656:Phenylephrine; D007545:Isoproterenol; D003000:Clonidine