. Effect of age on cutaneous vasoconstrictor responses to norepinephrine in humans. Am J Physiol Regul Integr Comp Physiol 287: R1230 -R1234, 2004 doi:10.1152/ajpregu.00467. 2004.-To test the hypothesis that cutaneous vasoconstrictor responsiveness to exogenous norepinephrine is reduced in older compared with young subjects, dose-response relations between norepinephrine and skin blood flow were established. Seven doses of norepinephrine (1 ⅐ 10 Ϫ8 to 10 Ϫ2 log M) were perfused (2 l/min) intradermally (4 min/dose) using cutaneous microdialysis (2 probes/subject). To account for possible differences in endogenous norepinephrine between groups, one microdialysis probe was perfused with bretylium tosylate to locally block noradrenergic vesicle release before establishing the norepinephrine dose-response relations. Skin blood flow was indexed via laser-Doppler flowmetry directly over both microdialysis probe sites and is expressed as cutaneous vascular conductance (laserDoppler flux/mean arterial blood pressure). Local skin temperature was maintained at 34°C at both sites throughout the protocol. Doseresponse relation between norepinephrine and cutaneous vascular conductance was similar between control and bretylium-pretreated sites in young subjects (EC 50 ϭ Ϫ5.18 Ϯ 0.27 and Ϫ5.03 Ϯ 0.27 log M, respectively). In contrast, the dose-response relation was significantly shifted to the right (i.e., a higher dose of norepinephrine was needed to produce the same vasoconstrictor response) in the bretylium-pretreated site in older subjects (EC 50 ϭ Ϫ5.46 Ϯ 0.23 and Ϫ4.53 Ϯ 0.23 log M, respectively). Significant increases in EC 50 were observed in older compared with young subjects at the bretylium-pretreated but not the control sites. These data indicate that cutaneous vasoconstrictor responsiveness is decreased in older subjects when endogenous release of norepinephrine is antagonized. Furthermore, these findings suggest that differences in presynaptic norepinephrine release between older and younger subjects are profound enough to affect dose-response relations between norepinephrine and cutaneous vascular conductance. intradermal microdialysis; ␣-adrenergic receptors; cold stress AGING modulates autonomic thermoregulatory responses during environmental stress (14,34,35). Reduced cutaneous vasodilation and sweating during heat stress are well established in older subjects (10,12,17,19,24). However, the effects of age on autonomic responses to cold stress are less clear. This lack of clarity is especially apparent when assessing age-related cutaneous vasoconstrictor responses.Kenney and Armstrong (13) have identified impaired rate and extent of forearm vasoconstriction in older subjects during a 120-min cold air stress. Although the mechanisms responsible for this vasoconstrictor deficit were not identified in this study, one possible mechanism for this impaired vasoconstrictor response in older adults could involve blunted end-organ responsiveness. Supporting this concept, Dinenno et al. (4) observed blunted vasoconstri...