Aging and cardiac responses to epinephrine in humans: role of neuronal uptake.
In healthy humans, ganglionic blockade unmasks a clear age-related decrease in cardiac responses to isoproterenol but not to epinephrine. We postulated that an age-related decrease in neuronal uptake (which affects epinephrine but not isoproterenol) may offset a parallel decrease in beta-receptor-mediated responses. To test this concept, nine young (mean 29 +/- 2 yr) and eight older (mean 61 +/- 2 yr) healthy subjects were infused on three different study mornings with epinephrine at increasing rates either alone or combined with desipramine to eliminate differences in neuronal uptake or with desipramine and trimetaphan to induce ganglionic blockade and thereby also eliminate differences in arterial baroreflex activity. Epinephrine caused the expected rate-related increases in systolic blood pressure, heart rate, stroke volume, ejection fraction, and cardiac index. Except for the systolic blood pressure, the extent of the changes was similar in young and older subjects. After desipramine, cardiac responsiveness to epinephrine was markedly enhanced, although more (P < 0.01) in young vs. older subjects for heart rate and cardiac index (+14 vs. 7 beats/min and +1.6 vs. 1.1 l.min(-1).m(-2), respectively, at 20 ng.kg(-1).min(-1)). Combined with desipramine and trimetaphan, cardiac responses to epinephrine were further enhanced, again more (P < 0.01) in young subjects, resulting in large differences in heart rate and ejection fraction increases (+29 vs. 17 beats/min and +14 vs. 7%, respectively, at 20 ng.kg(-1).min(-1)). Here, we show that "healthy aging" in humans is associated with decreased cardiac responsiveness to the beta-agonist epinephrine; however, this decrease can be balanced by concomitant decreases in buffering of these responses by neuronal uptake and the arterial baroreflex.
Leenen
Frans H H
FH
Hypertension Unit, University of Ottawa Heart Institute, Ottawa, Ontario, Canada. fleenen@ottawaheart.ca <fleenen@ottawaheart.ca>
Coletta
Elizabeth
E
Fourney
Anne
A
White
Roselyn
R
D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D017704:Baroreflex / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D003891:Desipramine / Q000008:administration & dosage; D004357:Drug Synergism; D004837:Epinephrine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D005730:Ganglionic Blockers / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D014294:Trimethaphan / Q000008:administration & dosage
D018759:Adrenergic Uptake Inhibitors; D000318:Adrenergic beta-Agonists; D005730:Ganglionic Blockers; D014294:Trimethaphan; D003891:Desipramine; D004837:Epinephrine