Skin Sympathetic Nerve Activity Responses Research Articles

Sympathoexcitation causes differing responses in supraorbital vs. peripheral skin nerves: implications for rosacea

Previous studies indicate that common fibular, tibial, and radial skin sympathetic nerve activity (SSNA) increases with physical stress in an exercise intensity-dependent manner but abates during ischemia when class III & IV muscle afferents are stimulated without the engagement of the motor cortex. It is currently unknown if these peripheral nerve responses are similar to those of facial nerves. Rosacea, a facial flushing disorder, results in substantially higher physical and mental stress-induced increases in SSNA, but whether this level of SSNA is modifiable is unknown. We tested the hypotheses that physical stress increases supraorbital SSNA in an intensity-dependent manner and that post-exercise muscle ischemia (PEMI) does not modulate supraorbital SSNA. Nine healthy subjects (5M/4F) participated in a series of physical stressors known to be symptom-triggering in individuals with rosacea. Forehead SSNA (supraorbital microneurography) was measured during handgrip exercise for 1 minute at 15%, 30%, and 45% of maximum hand grip strength. Additionally, 2 minutes of handgrip at 30% of maximum, followed by 2 minutes of PEMI (upper-arm arterial occlusion) were completed to assess the role of muscle afferents in the SSNA response. Skin blood flow (laser-Doppler flowmetry) and transepithelial water loss/sweat rate (TEWL/SR; capacitance hygrometry) were measured on both the forehead and the ventral forearm during procedures. Heart rate (HR; ECG) and mean arterial pressure (MAP; finger photoplethysmography) were also recorded. All intensities of handgrip increased HR and MAP, and these responses were positivity correlated with intensity. Handgrip also increased SSNA, but there was no association with intensity. No changes in skin blood flow or TEWL/SR were observed across trials. PEMI maintained handgrip-induced elevations of MAP and SSNA, albeit at a reduced magnitude compared to baseline. Contrary to our hypothesis, physical stress did not increase supraorbital SSNA in an intensity-dependent manner (15%, 30%, and 45% of maximum handgrip strength). Furthermore, unlike peripheral SSNA which increases during physical stress but abates during PEMI, these data indicate that ischemia or ischemic pain increases supraorbital SSNA. These data imply that supraorbital SSNA differs in control and regulation from peripheral nerves, and these differences could potentially account for altered supraorbital SSNA results observed in individuals with rosacea.

Augmented supraorbital skin sympathetic nerve activity responses to symptom trigger events in rosacea patients.

Facial flushing in rosacea is often induced by trigger events. However, trigger causation mechanisms are currently unclear. This study tested the central hypothesis that rosacea causes sympathetic and axon reflex-mediated alterations resulting in trigger-induced symptomatology. Twenty rosacea patients and age/sex-matched controls participated in one or a combination of symptom triggering stressors. In protocol 1, forehead skin sympathetic nerve activity (SSNA; supraorbital microneurography) was measured during sympathoexcitatory mental (2-min serial subtraction of novel numbers) and physical (2-min isometric handgrip) stress. In protocol 2, forehead skin blood flow (laser-Doppler flowmetry) and transepithelial water loss/sweat rate (capacitance hygrometry) were measured during sympathoexcitatory heat stress (whole body heating by perfusing 50°C water through a tube-lined suit). In protocol 3, cheek, forehead, forearm, and palm skin blood flow were measured during nonpainful local heating to induce axon reflex vasodilation. Heart rate (HR) and mean arterial pressure (MAP) were recorded via finger photoplethysmography to calculate cutaneous vascular conductance (CVC; flux·100/MAP). Higher patient transepithelial water loss was observed (rosacea 0.20 ± 0.02 vs. control 0.10 ± 0.01 mg·cm(-2)·min(-1), P < 0.05). HR and MAP changes were not different between groups during sympathoexcitatory stressors or local heating. SSNA during early mental (32 ± 9 and 9 ± 4% increase) and physical (25 ± 4 and 5 ± 1% increase, rosacea and controls, respectively) stress was augmented in rosacea (both P < 0.05). Heat stress induced more rapid sweating and cutaneous vasodilation onset in rosacea compared with controls. No axon reflex vasodilation differences were observed between groups. These data indicate that rosacea affects SSNA and that hyperresponsiveness to trigger events appears to have a sympathetic component.

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

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. 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. We additionally show that cutaneous vascular responsiveness to adrenergic stimuli is not reduced in older adults. These results further our understanding of the physiological mechanisms underlying impaired thermal-cardiovascular integration in healthy ageing. 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±1years) and 12 older adults (O; 57±2 years) participated in two protocols. In Protocol1, 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 (Tsk ) 30.5°C; water-perfused suit). Mental stress was performed at mean Tsk 34.0°C (thermoneutral) and at 30.5°C. In Protocol2, 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 (ΔCVCbase ). 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 Tsk 30.5°C further increased SSNA in both groups. There was no age-related difference in adrenergic responsiveness to exogenous NA (logEC50 :-6.41±0.24 inY, -6.37±0.25in 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.

Regional differences in sympathetic activation in lean and obese normotensive individuals with obstructive sleep apnoea

Obstructive sleep apnoea (OSA) is characterized by a marked sympathetic overdrive, as documented by the elevated sympathetic nerve firing rate detected in peripheral muscle nerves. No data are available, however, on the behaviour of sympathetic drive in vascular regional districts other than the muscle circulation. In 66 middle-aged normotensive individuals classified according to BMI, waist-to-hip ratio and apnoea-hypopnea index as lean individuals without (n = 20) or with (n = 14) OSA and as obese individuals without (n = 13) or with (n = 19) OSA, we measured blood pressure, heart rate, muscle sympathetic nerve activity (MSNA) and skin sympathetic nerve activity (SSNA), respectively, via microneurography. Measurements also included SSNA responses to an emotional stimulus. The four groups were matched for age, sex and blood pressure values. Both in lean and obese individuals, presence of OSA was accompanied by MSNA values significantly greater than those found in non-OSA individuals. In contrast, no significant difference was found in SSNA values between OSA and non-OSA patients both in the lean and in the obese groups. This was the case also for the SSNA responses to an emotional arousal. These data provide the first evidence that in OSA, the adrenergic overdrive seen in the muscle circulation is not detected in cutaneous circulation and thus it cannot be regarded as a generalized phenomenon affecting the whole cardiovascular system. Further studies are needed to clarify whether in OSA, sympathetic drive of other vascular districts, such as the coronary, renal or cerebral circulation, is activated or normal.

Abstract 528: Response of Muscle Sympathetic Nerve Activity to Heat Stress is Attenuated in Chronic Heart Failure

Cutaneous vascular conductance (CVC) rises during heat stress in normal humans. Recently, we showed that this response is attenuated in chronic heart failure (CHF), even though the skin sympathetic nerve activity response to heat stress was not attenuated. Of note, heat stress evokes significant increases in muscle sympathetic nerve activity (MSNA) in healthy individuals. This effect may allow flow to be distributed to other tissues. The MSNA response to heat stress in CHF has not been reported. We postulated that in CHF the MSNA response to heat stress is attenuated. Passive whole body heating was applied with water-perfused suits on 9 male (60 ± 3 yrs) patients with stable class II-III CHF and 9 age-matched male healthy subjects. Whole body heating induced similar increases in skin temperature (~4 °C), internal temperature (~0.6 °C), similar reduction in blood pressure, and similar increase in heart rate. The elevation in forearm CVC in CHF patients was significantly lower than that in healthy control subjects (102 ± 29 vs. 312 ± 54 units, P &lt; 0.001). While baseline MSNA in CHF was higher than in controls ( P &lt; 0.05); heat stress increased MSNA in the controls (33.2 ± 3.8 to 47.3 ± 4.4 bursts/min; 618 ± 74 to 934 ± 93 units/min, both P &lt; 0.001, N = 9), but not in CHF (43.4 ± 5.7 to 49.6 ± 7.0 bursts/min; 996 ± 104 to 1039 ± 108 units/min, both P &gt; 0.15, N = 6; two-factor ANOVA with repeated measure on one factor). Moreover, the MSNA change by heating in CHF was significantly lower than that in the controls (6.2 ± 2.6 to 14.1 ± 1.5 bursts/min; 43 ± 45 to 316 ± 34 units/min; both P &lt; 0.01, unpaired t-test). The attenuated MSNA response to heating was not due to a ceiling effect as that static fatiguing handgrip in CHF in a control trial evoked significant increases in MSNA. These data show that the MSNA response to heat stress is attenuated in CHF patients. We postulate that the attenuated MSNA response contributes to an impaired re-distribution of blood low to the skin during heat stress in CHF.

Melatonin attenuates the skin sympathetic nerve response to mental stress

Melatonin attenuates muscle sympathetic nerve responses to sympathoexcitatory stimuli, but it is unknown whether melatonin similarly attenuates reflex changes in skin sympathetic nerve activity (SSNA). In this double-blind, placebo-controlled, crossover study, we tested the hypothesis that melatonin (3 mg) would attenuate the SSNA response to mental stress (mental arithmetic). Twelve healthy subjects underwent experimental testing on two separate days. Three minutes of mental stress occurred before and 45 min after ingestion of melatonin (3 mg) or placebo. Skin temperature was maintained at 34°C. Reflex increases in SSNA (peroneal nerve), mean arterial pressure, and heart rate (HR) to mental stress before and after melatonin were determined. Melatonin lowered HR (pre, 66 ± 3 beats/min; and post, 62 ± 3 beats/min, P = 0.046) and SSNA (pre, 14,282 ± 3,706 arbitrary units; and post, 9,571 ± 2,609 arbitrary units, P = 0.034) at rest. In response to mental stress, SSNA increases were significantly attenuated following melatonin ingestion (second minute, 114 ± 30 vs. 74 ± 14%; and third minute, 111 ± 29 vs. 54 ± 12%, both P < 0.05). The mean arterial pressure increase to mental stress was blunted in the third minute (20 ± 2 vs. 17 ± 2 mmHg, P = 0.032), and the HR increase was blunted in the first minute (33 ± 3 vs. 29 ± 3 beats/min, P = 0.034) after melatonin. In summary, exogenous melatonin attenuates the SSNA response to mental stress.

Effect of mental stress on skin sympathetic nerve activity: Are responses reproducible?

The primary aim of this study was to quantify the effect of mental stress (MS) on skin sympathetic nerve activity (SSNA). There is limited quantitative data showing SSNA response to MS. Previous studies report divergent MSNA responses to MS. The second aim was to determine the reproducibility of SSNA to MS within a given day and 1 week later. Ten subjects (26±1 yr.) performed two bouts of mental arithmetic lasting 3 min. The bouts were separated by 45 min. One week later the subjects returned to repeat MS. All experiments were conducted in the supine posture during the morning hours. To maintain neutral skin temperature, each subject wore a custom suit (34–35°C). Skin blood flow and sweat rate were measured on the dorsal foot. MS elicited a marked increase in SSNA within the first 10 s (184±42%; P&lt;0.01) in all subjects, which was less during the remaining period of MS but remained elevated (87±20; P&lt;0.01). The pattern of responses to MS was unchanged during the second bout (10 s, 247±55%; 3 min avg., 133±29%) and during the retest 1 week later (10 s, 196±55%; 3 min avg., 117±36%). MS did not significantly affect cutaneous vascular conductance and sweat rate during any trial. In summary, MS elicits robust and reproducible increases in SSNA in humans. Thus unlike MS effect on MSNA, the pattern of SSNA is consistent during repeated trials on the same day and when performed 1 week later.Supported by NIH (HL109952)

Chronic Heart Failure Does Not Attenuate the Total Activity of Sympathetic Outflow to Skin During Whole-Body Heating

Previous studies show that the rise in skin blood flow and cutaneous vascular conductance during heat stress is substantially attenuated in chronic heart failure (CHF) patients. The mechanisms responsible for this finding are not clear. In particular, little is known regarding the responses of skin sympathetic nerve activity (SSNA) that control the skin blood flow during heat stress in CHF patients. We examined the effects of a modest heat stress to test the hypothesis that SSNA responses could be attenuated in CHF. We assessed SSNA (microneurography) from the peroneal nerve and skin blood flow (forearm laser Doppler) in 9 patients with stable class II-III CHF and in matched healthy subjects during passive whole-body heating with a water-perfused suit. Whole-body heating induced similar increases in internal temperature (≈0.6 °C) in both groups. Whole-body heat stress evoked similar SSNA activation in CHF patients (Δ891±110 U/min) and the control subjects (Δ787±84 U/min; P=0.66), whereas the elevation in forearm cutaneous vascular conductance in patients with CHF was significantly lower than that in healthy control subjects (Δ131±29% vs. Δ623±131%; P=0.001). The present data show that SSNA activation during a modest whole-body heat stress is not attenuated in CHF. Thus, the attenuated skin vasodilator response in CHF patients is not attributable to a reduction in total activity of sympathetic outflow to skin.

Augmented supraorbital skin sympathetic nerve activity responses to symptom trigger events in rosacea patients

To investigate if rosacea alters skin sympathetic nerve activity (SSNA) and end‐organ responses, 12 patients and age‐ and sex‐matched controls underwent 2 symptom triggering stressors (mental and physical stress). Subjects performed 2‐min mental arithmetic and 2‐min isometric handgrip (35% of maximal voluntary contraction). SSNA (supraorbital microneurography), forehead skin blood flow (laser‐Doppler flowmetry), and forehead sweat rate (capacitance hygrometry) were measured. Heart rate and mean arterial pressure (MAP) were recorded via finger photoplethysmography. Cutaneous vascular conductance (CVC) was calculated by flux/MAP, and SSNA was normalized to baseline. Heart rate and MAP changes from baseline were not different between patients and controls during either stressor. Rosacea patients showed higher baseline sweat rate than controls (0.20±0.02 vs. 0.10±0.02 mg/cm2/min, p&gt;0.05), and CVC trended higher compared to controls. SSNA during mental stress was higher in patients compared to controls (39±12% vs. 9±3%, p&gt;0.05); similar augmented SSNA responses were observed during handgrip (rosacea = 31±13% and controls = 2±1%, p&gt;0.05). These data identify trigger induced hyper‐responsiveness of sympathetic outflow in the face of rosacea patients and thus may be part of the etiology of the disease.Funded by a grant from the National Rosacea Society.

Skin Sympathetic Nerve Activity Response to Heat Stress in Congestive Heart Failure

BACKGROUND: Previous studies show that the rise in skin blood flow (SkBF) during heat stress is substantially attenuated in congestive heart failure (CHF) patients when compared to healthy subjects. However, the mechanism(s) leading to the attenuated rise in SkBF in CHF patients with heat stress is not clear. Both local mechanisms and central mechanism (i.e. skin sympathetic nerve activity, SSNA) may play a role in control of SkBF in heat stress. However, the SSNA response to heat stress in CHF has not been reported. PURPOSE: To examine the hypothesis that whole body heat stress does not cause any increase in SSNA in CHF. METHODS: We assessed SSNA (microneurography) from peroneal nerve and forearm SkBF (laser Doppler) in 7 patients with stable class II-III CHF and in healthy subjects during passive whole body heating with water perfused suit. RESULTS: Whole body heating induced a similar increase in internal temperature (∼0.7 °C) in all groups. The elevation in forearm cutaneous vascular conductance (CVC) in patients with CHF was significantly lower than that in healthy control subjects (233±37 vs. 852±176% of normothermic baseline (100%; P<0.001). Heat stress increased SSNA in CHF patients (100 to 239±29% of normothermic baseline, P<0.05) and healthy controls (100 to 369±74% of normothermic baseline, P<0.001). However, the CVC/SSNA in heat in CHF was lower than the healthy subjects (1.23±0.08 vs. 2.93±0.60, P<0.05). CONCLUSIONS: The data showed that SSNA was activated in CHF patients with whole body heating, however, lower CVC/SSNA in CHF may suggest an impaired cutaneous vasodilator response to the nerve activity. Supported by AHA 0635245 N, NIH P01 HL077670, and M01 RR010732.

Determinants of skin sympathetic nerve responses to isometric exercise

Exercise-induced increases in skin sympathetic nerve activity (SSNA) are similar between isometric handgrip (IHG) and leg extension (IKE) performed at 30% of maximal voluntary contraction (MVC). However, the precise effect of exercise intensity and level of fatigue on this relationship is unclear. This study tested the following hypotheses: 1) exercise intensity and fatigue level would not affect the magnitude of exercise-induced increase in SSNA between IHG and IKE, and 2) altering IHG muscle mass would also not affect the magnitude of exercise-induced increase in SSNA. In protocol 1, SSNA (peroneal microneurography) was measured during baseline and during the initial and last 30 s of isometric exercise to volitional fatigue in 12 subjects who randomly performed IHG and IKE bouts at 15, 30, and 45% MVC. In protocol 2, SSNA was measured in eight subjects who performed one-arm IHG at 30% MVC with the addition of IHG of the contralateral arm in 10-s intervals for 1 min. Exercise intensity significantly increased SSNA responses during the first 30 s of IHG (34+/-13, 70+/-11, and 92+/-13% change from baseline) and IKE (30+/-17, 69+/-12, and 76+/-13% change from baseline) for 15, 30, and 45% MVC. During the last 30 s of exercise to volitional fatigue, there were no significant differences in SSNA between exercise intensities or limb. SSNA did not significantly change between one-arm and two-arm IHG. Combined, these data indicate that exercise-induced increases in SSNA are intensity dependent in the initial portion of isometric exercise, but these differences are eliminated with the development of fatigue. Moreover, the magnitude of exercise-induced increase in SSNA responses is not dependent on either muscle mass involved or exercising limb.

Is Vestibular Activation a Nonthermal Modulator of Skin Blood Flow or Sweating?

2139 The cutaneous vasculature and eccrine sweat glands are modified by both thermal and nonthermal factors. PURPOSE: The purpose of this study was to determine if vestibular activation is a nonthermal modulator of skin sympathetic nerve activity (SSNA) and cutaneous end-organ responses. METHODS: 10 subjects performed static head-down rotation (HDR) and dynamic yaw and pitch (30 cycles•min-1) to activate otolith organs and semicircular canals. Body temperature, SSNA (peroneal microneurography), cutaneous vascular conductance (CVC; laser-Doppler flux/mean arterial pressure) and sweat rate within an area of innervated skin were measured during normothermia and after whole-body heating. RESULTS: During normothermia HDR did not significantly alter SSNA (Δ-0.4 ± 4.4 %), CVC (Δ4.2 ± 6.9 %) or sweat rate (Δ-2.7 ± 1.2 %). Whole-body heating significantly increased internal temperature (36.3 ± 0.1 to 37.1 ± 0.1 °C), mean skin temperature (32.8 ± 0.1 to 36.9 ± 0.3 °C), CVC (100 to 422 ± 109 %), and sweat rate (0 to 0.40 ± 0.08 mg/cm2/min). HDR during whole-body heating did not significantly affect SSNA (Δ3.2 ± 7.6 %), CVC (Δ-7.3 ± 3.9 %) or sweat rate (Δ-3.3 ± 1.9 %). Dynamic yaw and pitch also did not significantly alter SSNA, CVC, or sweat rate during normothermia or after whole-body heating. CONCLUSION: These data indicate vestibular activation is not a nonthermal factor modulating SSNA or cutaneous end-organ responses. Supported by NIH (DC6454), NSBRI (CA00207), and AHA (Established Investigator Grant and Beginning Grantin-Aid)

Vestibular activation does not influence skin sympathetic nerve responses during whole body heating.

The cutaneous vasculature and eccrine sweat glands are modified by both thermal and nonthermal factors. To determine the effect of thermal stress on the vestibulosympathetic reflex, skin sympathetic nerve activity (SSNA) and cutaneous end-organ responses were measured in 10 subjects during static head-down rotation (HDR) and dynamic yaw and pitch (30 cycles/min) to activate the otolith organs and semicircular canals. SSNA (microneurography of peroneal nerve), cutaneous vascular conductance (CVC; laser-Doppler flux/mean arterial pressure), sweat rate (capacitance hygrometry), and body temperature were collected during normothermia and after whole body heating. Body temperature was controlled by perfusing neutral (34-35 degrees C) or warm (44-46 degrees C) water through a tube-lined suit. During normothermia, HDR did not alter SSNA (-0.4 +/- 4.4% change), CVC (4.2 +/- 6.9% change), or sweat rate (-2.7 +/- 1.2% change) within the innervated area of skin. Dynamic yaw and pitch also did not elicit significant changes in SSNA, CVC, or sweat rate during normothermia. Whole body heating significantly increased internal temperature (0.8 +/- 0.1 degrees C), mean skin temperature (4.1 +/- 0.2 degrees C), CVC (322 +/- 109% control), and sweat rate (0.35 +/- 0.08 mg.cm(-2).min(-1)). After whole body heating, HDR did not significantly alter SSNA (3.2 +/- 7.6% change), CVC (-7.3 +/- 3.9% change), or sweat rate (-3.3 +/- 1.9% change). Dynamic yaw and pitch also did not produce significant changes in SSNA, CVC, or sweat rate after whole body heating. These data suggest that vestibular activation by head movements is not a nonthermal factor affecting SSNA and cutaneous end-organ responses in humans.

Comparison of skin sympathetic nerve responses to isometric arm and leg exercise

Measurement of skin sympathetic nerve activity (SSNA) during isometric exercise has been previously limited to handgrip. We hypothesized that isometric leg exercise due to the greater muscle mass of the leg would elicit greater SSNA responses than arm exercise because of presumably greater central command and muscle mechanoreceptor activation. To compare the effect of isometric arm and leg exercise on SSNA and cutaneous end-organ responses, 10 subjects performed 2 min of isometric knee extension (IKE) and handgrip (IHG) at 30% of maximal voluntary contraction followed by 2 min of postexercise muscle ischemia (PEMI) in a normothermic environment. SSNA was recorded from the peroneal nerve. Cutaneous vascular conductance (laser-Doppler flux/mean arterial pressure) and electrodermal activity were measured within the field of cutaneous afferent discharge. Heart rate and mean arterial pressure significantly increased by 16 +/- 3 and 23 +/- 3 beats/min and by 22 +/- 2 and 27 +/- 3 mmHg from baseline during IHG and IKE, respectively. Heart rate and mean arterial pressure responses were significantly greater during IKE compared with IHG. SSNA increased significantly and comparably during IHG and IKE (52 +/- 20 and 50 +/- 13%, respectively). During PEMI, SSNA and heart rate returned to baseline, whereas mean arterial pressure remained significantly elevated (Delta12 +/- 2 and Delta13 +/- 2 mmHg from baseline for IHG and IKE, respectively). Neither cutaneous vascular conductance nor electrodermal activity was significantly altered by either exercise or PEMI. These results indicate that, despite cardiovascular differences in response to IHG and IKE, SSNA responses are similar at the same exercise intensity. Therefore, the findings suggest that relative effort and not muscle mass is the main determinant of exercise-induced SSNA responses in humans.

Effect of skin sympathetic response to local or systemic cold exposure on thermoregulatory functions in humans

We studied how sympathetic response to cold exposure determines thermoregulatory function. Three female and seven male volunteers (age, 23.2±1.9 years) were exposed to abrupt local cooling and gradual systemic cooling with recording of microneurographic skin sympathetic nerve activity (SSNA), skin temperatures ( T s), tympanic temperature ( T ty), skin blood flow measured by laser Doppler flowmetry, and sweating rate measured with a ventilated capsule. Local cooling induced an abrupt vasoconstrictor SSNA increase and T ty rise. There was a significant positive correlation between the increase in the vasoconstrictor SSNA and the change rate of T ty. Systemic cooling at 0.2°C/min enhanced SSNA but gradually decreased T ty, and a significant negative correlation was observed between them. A 10-min delay separated the SSNA rise from the subsequent T ty rise following local cooling. A delay of less than 1 min preceded the SSNA increase after the T ty fall induced by systemic cooling. These findings suggested that subjects with a good SSNA response to cold stress can maintain core temperature, but 10 min is necessary to raise the core temperature by reducing heat loss from the skin surface. In contrast, vasoconstrictor SSNA responds linearly to a fall in core temperature with a delay of less than 1 min.

Skin sympathetic neuroeffector response is attenuated dose-dependently by systemic prostaglandin E1 injection in humans

To clarify the effects of prostaglandin E1 (PGE1) on the vasoconstrictive responses, we compared the correlation between the amplitude of integrated skin sympathetic nerve activity (SSNA) and per cent reduction in skin blood flow (SBF) before and after the infusion of lipo PGE1 and placebo (bolus one-shot infusion, single blind study), and constant rate infusion of PGE1 (10 and 50 ng kg−1 min−1 by infusion pump, dose-dependency study) in ten healthy men. SSNA was recorded microneurographically from the median nerve simultaneously with SBF by laser Doppler flowmetry at the index fingertip. The measurement was conducted 30 min after injection of lipo PGE1 or placebo, and during the drip infusion of 10 and 50 ng kg−1 min−1 of PGE1 with maneuvers to enhance SSNA. The resting and activated skin blood flow were not significantly different between 10 ng lipo PGE1 and placebo administration, and between baseline and 10, 50 ng kg−1 min−1 of PGE1 injection. The vascular response, defined as the slope of regression line between logarithm of amplitude of integrated SSNA bursts and the reduction in SBF, was significantly suppressed by injection of lipo PGE1 as compared with that by placebo. It was also decreased dose-dependently by the constant rate infusion of PGE1 (10 and 50 ng kg−1 min−1). We concluded that the intravenous injection of PGE1 attenuates vasoconstrictive responses to SSNA, and analysis of the relations between SSNA and vasoconstrictive response, i.e. the neuroeffector response, is suggested to be an important tool to assess the drug effect.

Autonomic responses to environmental stimuli in human body.

The author reviewed in this paper current microneurographic findings on the responses of muscle sympathetic nerve activity (MSNA) and skin sympathetic nerve activity (SSNA) to the environment in humans with special reference to vibration-induced white finger (VWF). 1) MSNA was enhanced by +Gz gravitational input, while being suppressed by simulated weightlessness through the baroreflex mechanism to maintain hemodynamic homeostasis. 2) MSNA was enhanced by hypobaric hypoxia through the chemoreflex mechanism. 3) SSNA was lowest under thermoneutral ambient temperature condition. Sudomotor component of SSNA increased under hot ambient temperature, while vasomotor component of SSNA increased under cold ambient temperature. 4) MSNA and vasomotor component of SSNA increased by local cold stimuli such as when a hand was immersed into cold water. 5) SSNA was enhanced by local vibration of the human body. The vibratory frequency of 60 Hz was the most effective for vibration-induced SSNA response. With a constant vibratory frequency of 60 Hz, SSNA increased depending on the vibratory acceleration. MSNA was not enhanced by local vibration of the body. 6) SSNA was markedly enhanced by combined stimuli of local vibration and noise. 7) MSNA increased during handgrip exercise, presumably depending on afferent inputs from muscle metaboreceptors. 8) The sympathetic response to environmental stress was markedly influenced by aging. The basal level of MSNA increased with aging, while the MSNA responsiveness to gravitational stress became reduced by aging. MSNA responsiveness to simulated weightlessness was also reduced by aging. 9) Vibration-induced white finger may be related to complex autonomic dysfunctions including excessive somato-sympathetic reflex induced by local vibration, cold stimuli and handgrip exercise. Gravity-dependent sympathetic nerve responses and the influence of aging may also contribute to the underlying mechanisms of VWF.