Effect of age on cutaneous vasoconstrictor responses to norepinephrine in humans

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 . 10(-8) to 10(-2) log M) were perfused (2 mul/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 (laser-Doppler flux/mean arterial blood pressure). Local skin temperature was maintained at 34 degreesC at both sites throughout the protocol. Dose-response relation between norepinephrine and cutaneous vascular conductance was similar between control and bretylium-pretreated sites in young subjects (EC(50) = - 5.18 +/- 0.27 and - 5.03 +/- 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) = - 5.46 +/- 0.23 and - 4.53 +/- 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.