Impaired increases in skin sympathetic nerve activity contribute to age‐related decrements in reflex cutaneous vasoconstriction

Abstract

Key pointsr The reduction in skin blood flow during whole-body cooling is impaired in healthy older adults. However, the relative contributions of altered skin sympathetic nerve activity (SSNA), transduction of this efferent neural outflow to the cutaneous vasculature, and peripheral vascular responsiveness to adrenergic stimuli to the impaired reflex vasoconstrictor response to whole-body cooling in human ageing remain unclear.r We report that the SSNA response to whole-body cooling is blunted in healthy older adults, and this attenuated sympathetic response is related to a marked impairment in reflex cutaneous vasoconstriction. Further, the reflex SSNA response to a non-thermoregulatory stimulus was preserved in older adults during cooling.r We additionally show that cutaneous vascular responsiveness to adrenergic stimuli is not reduced in older adults.r These results further our understanding of the physiological mechanisms underlying impaired thermal-cardiovascular integration in healthy ageing.Abstract Reflex cutaneous vasoconstriction is impaired in older adults; however, the relative roles of altered skin sympathetic nerve activity (SSNA) and end-organ peripheral vascular responsiveness are unclear. We hypothesized that in older adults whole-body cooling would elicit a blunted SSNA response and cutaneous adrenergic responsiveness would be reduced. Twelve young adults (Y; 24 ± 1 years) and 12 older adults (O; 57 ± 2 years) participated in two protocols. In Protocol 1, SSNA (peroneal microneurography) and red cell flux in the affected dermatome (laser Doppler flowmetry; dorsum of foot) were measured during whole-body cooling (mean skin temperature (T sk ) 30.5°C; water-perfused suit). Mental stress was performed at mean T sk 34.0°C (thermoneutral) and at 30.5°C. In Protocol 2, an intradermal microdialysis fibre was placed in the skin of the lateral calf for graded infusions of noradrenaline (norepinephrine) (NA; 10 −12 to 10 −2 M). Cutaneous vascular conductance (CVC = flux/mean arterial pressure) was expressed as a change from baseline ( CVC base ). Vasoconstriction was attenuated in O. SSNA increased significantly during cooling in Y (+184 ± 37%; P < 0.05) but not O (+51 ± 12%; P > 0.05). Mental stress at T sk 30.5°C further increased SSNA in both groups. There was no age-related difference in adrenergic responsiveness to exogenous NA (logEC 50 : −6.41 ± 0.24 in Y, −6.37 ± 0.25 in O; P > 0.05). While the SSNA response to whole-body cooling is impaired with ageing, SSNA can be further increased by a non-thermoregulatory stimulus. Cutaneous adrenergic sensitivity is not reduced in O. These findings suggest that alterations in afferent signalling or central processing likely contribute to blunted SSNA responses to cooling and subsequent impairments in reflex cutaneous vasoconstriction in ageing. Abbreviations BP, blood pressure; CVC, cutaneous vascular conductance; MAP, mean arterial pressure; NA, noradrenaline (norepinephrine); SSNA, skin sympathetic nerve activity; T sk , skin temperature.

Purinergic Signaling in the Cardiovascular System

“…84 There is impaired sympathetic nerve activity to the skin in old age, which is related to impaired reflex vasoconstrictor responses to whole-body cooling in human aging, perhaps mediated by ATP. 85 ATP enhances cholinergic cutaneous vasodilation, but not sweating, in young males and females. 86 Adenosine receptors play a role in evoking the venous distension reflex in humans.…”

Sympathetic control of reflex cutaneous vasoconstriction in human aging

“…3). These increases in SSNA during cooling were closely correlated with reductions in skin blood flow (59), confirming that it is primarily an adrenergic vasoconstrictor neural stimulus during cold stress that evokes reflex peripheral vasoconstriction in young skin (11). However, as shown in Fig.…”

“…During whole body cooling, decreases in mean skin temperature to 30.5°C resulted in a robust increase in efferent skin sympathetic nerve activity (SSNA) in young adults (28,58,59,124) (Fig. 3).…”

“…3, the SSNA response to whole body cooling was substantially reduced in healthy older adults (Ͼϳ60 yr) (58,59). This diminished efferent sympathetic outflow directed to the skin contributes substantially to the age-related attenuation in reflex cutaneous vasoconstriction and the resultant relative inability of older adults to adequately reduce skin blood flow during whole body cold exposure (59).…”

“…To further examine potential age-related alterations in the central ability to elicit skin sympathetic outflow, Greaney et al (59) additionally assessed SSNA during the nonthermoregulatory stimulus of mental stress at both thermoneutrality and also during whole body cooling. Aged adults exhibited robust increases in SSNA during mental stress superimposed on whole body cooling (59).…”