Altered neurotransmitter control of reflex vasoconstriction in aged human skin

Abstract

Cutaneous vasoconstriction (VC) in response to cooling is attenuated in older humans; however, mechanisms underlying this functional decline remain unclear. The present study tested the hypothesis that the contributions of noradrenaline (NA) and sympathetic cotransmitters to reflex-mediated cutaneous VC are altered with age. In 11 young (18-26 years) and 11 older (61-77 years) men and women, forearm skin blood flow was monitored at three sites using laser Doppler flowmetry (LDF) while mean skin temperature was lowered from 34 to 30.5• C using a water-perfused suit. Cutaneous vascular conductance (CVC; LDF/mean arterial pressure) was expressed as percentage change from baseline (% ∆CVC base ). Solutions of yohimbine + propranolol (Y + P), bretylium tosylate (BT), and lactated Ringer solution were infused via intradermal microdialysis at each LDF site to antagonize α-and β-adrenoceptors, block sympathetic release of NA and cotransmitters, and act as control, respectively. During cooling, VC was attenuated at the control site in older subjects compared to young subjects (−16 ± 3 versus −34 ± 4% ∆CVC base , P < 0.001). Y + P attenuated VC in young subjects (−13 ± 8% ∆CVC base , P < 0.001 versus control) and abolished VC in older subjects (0 ± 3% ∆CVC base , P > 0.9 versus baseline). BT completely blocked VC in both age groups. Cutaneous VC in young subjects is mediated by both NA and sympathetic cotransmitter(s); however, reflex VC in aged skin is attenuated compared to young and appears to be mediated solely by NA.

Muscle sympathetic nerve activity during cold stress and isometric exercise in healthy older adults

“…Although the reason for these disparate findings remains unclear, differences may be related to varied methodology of the cooling perturbation, because the intensity and populations of thermal and/or pain receptors stimulated by the cooling para- digm are known to influence sympathetic outflow. To this end, the present investigation examined sympathetic nervous system activation in healthy young and older adults using a standardized whole body skin surface cooling protocol via water-perfused suit (3,30,51,55). Consistent with a wide body of literature examining MSNA at rest in older adults at thermoneutrality (27,39,53), older adults in the present study exhibited increases in basal muscle sympathetic outflow.…”

“…Intriguingly, studies also suggest an age-related impairment in tonic nitric oxide "buffering" of ␣ 2 -adrenergic receptor responsiveness (31) or perhaps diminished ␣ 2 -adrenergic receptor responsiveness reflective of more generalized reductions in nitric oxide bioavailability with aging (8). Furthermore, while the sympathetic cotransmitters NPY and ATP contribute to reflex cutaneous vasoconstriction in young adults, these mechanisms are functionally absent in healthy aging; therefore, older adults instead rely entirely on impaired adrenergic-mediated vasoconstriction during cold stress (55). Clearly, the interaction between sympathetic outflow and adrenergic receptor function during whole body cooling in the context of healthy aging requires further investigation.…”

“…This target mean Tsk is above the threshold for shivering for most adults (6), and shivering was not observed in either subject group in the present study. Because of the brevity of the skin surface cooling protocol, core temperature does not change significantly (25,55). Mean Tsk was then clamped at 30.5°C, and a second bout of static HG was performed, as described above.…”

“…Reflex cutaneous vasoconstriction is markedly attenuated in healthy older adults, likely mediated by impairments in both end-organ responsiveness (30,51,55) and the thermoregulatory control of skin sympathetic nerve activity (19). In young adults, whole body cold stress elicits a pronounced systemic pressor response (3,4,9,23,62), and this pressor response to mild cold stress (i.e., with no reduction in core body temperature) is exaggerated in aged humans (23,60).…”

Perspectives on Environmental Adaptability and Physiological Polymorphism in Thermoregulation

“…Generally, various transmitters are involved with vasoconstriction. It is reported that elderly people's vasoconstriction response mainly occurs by noradrenalin, and not by other transmitters (Thompson and Kenney, 2004).…”