Thompson, Caitlin S., Lacy A. Holowatz, and W. Larry Kenney. Cutaneous vasoconstrictor responses to norepinephrine are attenuated in older humans. Am J Physiol Regul Integr Comp Physiol 288: R1108 –R1113, 2005. First published January 20, 2005; doi:10.1152/ajpregu.00839.2004.—Cutaneous vasoconstriction (VC) in response to cooling is impaired with human aging. On the basis of previous findings that older humans rely predominantly on norepinephrine (NE) for reflex VC of skin blood vessels, and that the VC effects of NE are blunted with age in many vascular beds, we tested the hypothesis that cutaneous VC responses to exogenous NE are attenuated in aged skin compared with young skin. In 11 young (18–30 yr) and 11 older (62–76 yr) men and women, skin blood flow was monitored at two forearm sites with laser Doppler (LD) flowmetry, while local skin temperature was clamped at 34°C. At one site, five doses of NE (10 10 to 10 2 M) were sequentially infused via intradermal microdialysis while the other site served as control (C; Ringer). Cutaneous vascular conductance (CVC; LD flux/mean arterial pressure) was expressed as percent change from baseline (% CVCbase). At 10 , 10 , and 10 6 M NE, older VC responses were attenuated compared with young [10 : 35 (95% confidence interval: 16, 52) vs. 49 ( 40, 58) % CVCbase, P 0.02; 10 : 38 ( 20, 56) vs. 50 ( 40, 61) % CVCbase, P 0.03; 10 : 52 ( 35, 70) vs. 67 ( 60, 74) % CVCbase, P 0.01]. Older maximal VC responses were also blunted compared with young [ 80 (confidence interval: 73, 87) vs. 88 (confidence interval: 87, 90) % CVCbase, P 0.03]. NE-mediated cutaneous VC is blunted at both physiological and superphysiological doses in older subjects compared with young subjects. Considering that NE is the only functional neurotransmitter mediating reflex VC in aged skin, attenuated NE-mediated VC may further predispose older humans to excess heat loss in the cold.