Simplified measurement of norepinephrine kinetics: Application to studies of aging and exercise training

We assessed simplified approaches to measurement of steady-state norepinephrine (NE) kinetics (short, nonprimed infusions of [³H]NE or of unlabeled NE and arterialized venous sampling), then reexamined the kinetic mechanism(s) of the age-associated increase in plasma NE, and tested the hypothesis that the latter is the result of a sedentary lifestyle. We studied 17 young (21-28 yr) and 21 elderly (60-76 yr) subjects and a subset (n = 8) of the latter again after 1 yr of physical training. NE appearance rates (R(a)) and NE metabolic clearance rates (MCRs), calculated from arterialized venous data, were not significantly different from those calculated from arterial data, whereas those calculated from venous data were substantially (~50%) higher. NE R(a) and NE MCR, determined from infusions of unlabeled NE were ~20% higher than those determined with [³H]NE, a finding plausibly attributed to ~20% suppression of endogenous NE appearance. Arterialized venous plasma NE concentrations were significantly higher in the elderly as a result of significantly higher NE R(a) and lower NE MCR. However, arterial NE R(a) was not increased, and venous NE MCR was not decreased significantly in the elderly. In the subset of elderly subjects, 1 yr of physical training, which increased peak O₂ consumption by 24%, did not decrease plasma NE or NE R(a) or increase NE MCR. Therefore, 1) arterial sampling provides no practical advantage over arterialized venous sampling in the measurement of NE kinetics. 2) The use of unlabeled NE infusions to determine NE kinetics overestimates NE R(a) and NE MCR by ~20%. 3) Conclusions concerning the kinetic mechanism(s) of the age-associated increase in plasma NE are influenced by the sampling site. Both increased NE R(a) and decreased NE MCR are demonstrable with arterialized venous sampling. 4) Age-associated increments in NE are not the result of a sedentary lifestyle.