Age Differences in Plasma Norepinephrine Kinetics in Humans

To determine if the increased plasma norepinephrine (NE) of older individuals is due to greater plasma NE appearance rate and/or decreased NE clearance, arterialized plasma NE kinetics were measured in 25 healthy young (27 +/- 6 yr, M +/- SD) and 18 healthy older volunteers (68 +/- 5 yr) using a tritium-labeled NE isotope dilution technique. Basal NE levels were 54% greater in the older participants (282 +/- 24 vs. 183 +/- 11 pg/ml, M +/- SEM, p less than .001). The mean plasma NE appearance rate was 32% higher (0.33 +/- 0.03 vs. 0.25 +/- 0.02 microgram/m2/min, p less than .016) and NE clearance was 19% lower (1.21 +/- 0.08 vs. 1.49 +/- 0.06 L/min/m2, p less than .006) in the older participants. There was a close correlation between NE appearance rate and NE levels (r = .76, p less than .001, N = 43), but only modest inverse correlation between NE clearance and NE levels (r = -.37, p less than .01, N = 43). Stepwise multiple linear regression analysis revealed that NE appearance rate and clearance explained 80% of the variance in NE levels and that 57% of the variance was attributable to NE appearance, F (1,41) = 54.8, p less than .001, compared with only 14% by NE clearance, F (1, 41) = 6.5, p = .01. We conclude that the principal factor accounting for the higher plasma NE levels of older individuals is an increase in plasma NE appearance rate.