Interaction of sympathetic vasoconstriction and antidromic vasodilatation in the control of skin blood flow

 We studied the interaction between the vasoconstriction evoked by postganglionic sympathetic neurones (sympathetic vasoconstriction) and the vasodilatation mediated by small-diameter afferent neurones (antidromic vasodilatation) in hairless skin of anaesthetized rats kept under controlled conditions. In all animals both the lumbar sympathetic trunk (LST) and the ipsilateral dorsal root (DR) L5 were surgically exposed, sectioned and electrically stimulated using different protocols. This experimental approach results in the exclusive and selective activation of sympathetic efferents and primary afferents respectively. Blood flow responses were measured using laser Doppler flowmetry. Sectioning the LST resulted in a pronounced increase in cutaneous blood flow by 112±15% (mean±SEM, n=25) indicating that ongoing sympathetic vasoconstrictor activity had been abolished. When a brief antidromic vasodilatation was produced by DR stimulation with 10–15 pulses at 1 Hz with C-fibre intensity during a sustained sympathetic vasoconstriction, peak blood flow reached preconstriction levels at LST stimulation frequencies of ≤3 Hz. By contrast, antidromic vasodilatation was reduced at sympathetic stimulation frequencies of ≥5 Hz and absent when stimulating the LST with 20 Hz. A similar response characteristic was obtained when LST and DR stimulation were started simultaneously. Continuous DR stimulation with 0.1 Hz evoked a substantial increase in cutaneous blood flow by 38±10% (mean±SEM, n=8) to a new baseline level. When sympathetic vasoconstriction was elicited on this background DR stimulation, the responses were smaller at all sympathetic frequencies. However, the maximum decrease in blood flow was significantly smaller than the controls at LST stimulation with ≤3 Hz but not at higher frequencies. We conclude that sympathetic vasoconstriction and antidromic vasodilatation are competitive influences in the control of cutaneous blood flow. At low levels of cutaneous sympathetic vasoconstrictor activity, which probably prevail under resting conditions in the absence of cold stress, antidromic vasodilatation overrides sympathetic vasoconstriction. At high levels of cutaneous sympathetic activity, which may be reached in normal life under the conditions of severe cold, sympathetic vasoconstriction can suppress antidromic vasodilatation almost totally. Received: 24 April 1996 / Accepted: 3 September 1996     

Functional evidence for the differential control of superficial and deep blood vessels by sympathetic vasoconstrictor and primary afferent vasodilator fibres in rat hairless skin

We quantitatively investigated sympathetic vasoconstriction and antidromic vasodilation mediated by small-diameter primary afferents on the plantar hairless skin of the hindpaws in Wistar rats using laser Doppler (LD) flowmetry and an infrared thermometer. Sympathetic vasoconstriction was elicited by electrical stimulation of the centrally cut ipsilateral lumbar sympathetic trunk (LST) with 50-s trains at 0.1–20 Hz. Antidromic vasodilation was evoked by electrical stimulation of the dorsal root (DR) L5 with 20-s or 50-s trains at 1–4 Hz. Cutting the LST resulted in increases in skin temperature (SKT) by 6.1±1.0° C (mean±SEM) and in LD flow by 128±20%. Stimulation of the LST resulted in a graded decrease in LD flow and SKT that was most pronounced between 0 and 0.1 Hz. However, DR stimulation evoked a large increase in LD flow but only little change in SKT in rats with sectioned LST. When the DR was stimulated either in animals with intact LST or during continuous stimulation of vasoconstrictor fibres in the sectioned LST, i.e. while baseline temperature was relatively low (26.3±1.1° C), DR stimulation still resulted in large increases in LD flow, but only minor changes in SKT. These results suggest that blood flow through both deep and superficial layers of rat hairless skin is regulated by activity in sympathetic postganglionic vasoconstrictor fibres, whereas small-diameter primary afferent fibres appear to influence predominantly the blood flow through superficial layers of rat plantar skin. Received: 22 April 1997/Accepted: 11 July 1997     

Thermoregulatory adjustments of skin blood flow in chronically spinalized dogs

Summary In awake dogs chronically spinalized at the level of Th₃-Th₆, the isolated section of the spinal cord was selectively cooled or heated at low, constant ambient air temperatures. A decrease of the skin temperatures at one or both hindpaws indicating cutaneous vasoconstriction was induced in 5 out of 7 animals by the spinal cold stimulus. These observations were confirmed by measuring cutaneous heat conductivity of the hindpaws. Selective heating of the spinal cord only occasionally induced a cutaneous vasodilatation.At the low ambient temperature conditions, the vasoconstriction induced by the spinal cold stimulus sometimes did persist after the end of spinal cord cooling. This indicated that peripheral cold stimuli also could induce reflex vasoconstrictor activity in the isolated spinal cord.The observations made on the influence of central cold stimuli on cutaneous blood flow in the spinalized animal contribute further support to the hypothesis that basic properties for thermoregulatory performance are established in spinal neuronal networks.Part of this work was presented at the 35. Congress of the Deutsche Physiologische Gesellschaft, 26.–28. März 1969 [Pflügers Arch.307, R 98 (1969)].     

Physiological blushing in social anxiety disorder patients with and without blushing complaints: Two subtypes?

This study investigates whether social anxiety disorder (SAD) patients with blushing complaints show heightened physiological blushing and arousability in social situations than SAD patients without blushing complaints and healthy controls. SAD blushers (n = 32), SAD non-blushers (n = 34), and healthy controls (n = 25) conducted two social tasks. The physiological responses cheek and forehead blood flow, cheek temperature, and skin conductance were recorded, as well as confederates-observed blushing. The SAD blushers showed more physiological blushing (cheek temperature and blood flow) than SAD non-blushers and observers detected this difference. This finding was also present in comparison to the controls, except for blood flow. For blood flow SAD blushers and controls did not differ but SAD non-blushers showed a ‘suppressed response’: a smaller cheek blood flow increase during the interaction and no recovery compared to the other groups. Furthermore, on skin conductance no differences between groups were observed. Discussed is to what extent SAD blushers and SAD non-blushers represent two qualitative distinct subgroups of SAD.     

Laser-Doppler and plethysmographic skin blood flow during exercise and during acute heat stress in the sauna

Summary Forearm skin blood flow was measured in six male subjects by laser-Doppler flowmetry (LDF) and venous occlusion plethysmography (VOP) during constant-load (125–200 W) upright bicycle exercise in a warm environment ( + SD,t _a 34.6±0.2‡ C) and during a 15 min sauna bath (t _a 69.0±2.8‡ C). During the sauna test the LDF values correlated well with the VOP measurements in the initial phase of active cutaneous va-sodilation, after which the LDF values almost leveled off in spite of a steady increase in VOP measurements. During the exercise the mean VOP and LDF values rose in parallel with each other to steady state levels. The relationship between the results of the two methods proved to be nonlinear. It was concluded that different parameters were measured by VOP and LDF. The latter measured mainly the integrated velocity of blood flow in the outermost cutaneous tissue, and this velocity seemed to be partly dependent on the level of the arterial inflow (VOP), but also on the prevailing pressure-flow and pressure-volume relations in the cutaneous vascular bed.     

Effects of deep and superficial experimentally induced acute pain on skin sympathetic nerve activity in human subjects

There is evidence in experimental animals that deep and superficial pain exert differential effects on cutaneous sympathetic activity. Skin sympathetic nerve activity (SSNA) was recorded from the common peroneal nerve of awake human subjects and injections of 0.5 ml hypertonic saline was made into the tibialis anterior muscle (causing a deep, dull ache) or 0.2 ml into the overlying skin (causing a sharp burning pain) at unexpected times. Both deep and superficial pain caused increases in SSNA immediately on injection and preceding the onset of pain for both muscle and skin pain (10.1 ± 2.4 vs. 15.3 ± 5.3 s; muscle versus skin, respectively). SSNA increases were short lasting (104.2 ± 13.4 vs. 81.8 ± 11.7 s; muscle versus skin pain) and did not follow muscle and skin pain profiles. Sweat release occurred following both intramuscular and subcutaneous injections of hypertonic saline. While muscle or skin pain invariably caused changes in skin blood flow as well as increases in sweat release, skin blood flow increased in females and decreased in males. We conclude that both acute muscle and skin pain cause an increase in SSNA, sweat release and gender-dependent changes in skin blood flow.     

Different vascular responses in glabrous and nonglabrous skin with increasing core temperature during exercise

To elucidate the characteristics of vasomotor control in glabrous and nonglabrous skin during dynamic exercise, we compared the vascular responses in both areas to increasing core temperature during the cycle exercise for 30 min at different intensities in the range 20–60% of peak oxygen consumption (VO_2peak) in a total of 13 male and four female subjects in two experimental protocols. Skin blood flow was monitored using laser Doppler flowmetry. In protocol 1, the slope of the relationship between esophageal temperature (T _es) and cutaneous vascular conductance (CVC) in the early phase of the exercise decreased (P < 0.05) with increasing exercise intensity at glabrous sites (palm) but not nonglabrous sites (dorsal hand). In protocol 2, to examine whether a difference in vascular responses in the two areas is due to the adrenergic vasoconstrictor system, the release of norepinephrine from adrenergic nerves in forearm and palmar skin was blocked locally by iontophoresis of bretylium tosylate (BT). The administration of BT diminished completely the change of CVC in the palm during the exercise but did not alter the response in the forearm compared with the untreated site. In the two areas, neither the T _es threshold for vasodilation nor the change in CVC above the threshold in the middle and late phase of the exercise was influenced by the intensity of the exercise. These results suggest that, in the early phase of the exercise, light-to-moderate exercise reduces in an intensity-dependent manner the thermal sensitivity for vasodilation in glabrous skin but not nonglabrous skin via an adrenergic vasoconstrictor pathway.     

Mild hypohydration induced by exercise in the heat attenuates autonomic thermoregulatory responses to the heat, but not thermal pleasantness in humans

Hypohydration caused by exercise in the heat attenuates autonomic thermoregulation such as sweating and skin blood flow in humans. In contrast, it remains unknown if behavioral thermoregulation is modulated during hypohydration. We assume that thermal unpleasantness could drive the behavioral response, and would also be modulated during hypohydration. Nine healthy young men participated in the present study. Body and skin temperatures were monitored. Ratings of thermal sensation and pleasantness were conducted. After ∼ 45 min rest at 27 °C, they performed 50-min cycling exercise, which was at the level of 40% of heart rate range at 35 °C (hypohydration trial) or at the level of 10% of heart rate range at 23 °C (control trial), respectively. Subjects returned to the rest at 27 °C, and the ambient temperature was then changed from 22 to 38 °C. Body weight decreased by 0.9 ± 0.1% immediately after exercise in the hypohydration trial and 0.3 ± 0.1% in the control trial. In the cold, no significant difference in thermal sensation or pleasantness was observed between trials. There was no significant difference in thermal pleasantness between trials in the heat, although thermal sensation in the heat (32.5-36 °C) was significantly lower in the hypohydration trial than in the control trial. In addition, laser Doppler flow of the skin and sweat rate were attenuated in the heat in the hypohydration trial. These results may indicate that mild hypohydration after exercise in the heat has no influence on behavioral responses to the heat.     

Skin blood flow changes in anaesthetized humans: comparison between skin thermal clearance and finger pulse amplitude measurement

Summary The effect of general anaesthesia on skin blood flow in the left hand, measured by a new non-invasive probe using the thermal clearance method was examined. A mercury silastic gauge was placed around the third left finger and the plethysmographic wave amplitude was recorded to measure changes in finger pulse amplitude. Heart rate (HR), mean arterial blood pressure (MABP) and skin temperature were also recorded. General anaesthesia was induced by droperidol and phenoperidine injection and propanidid infusion in eight female patients. Skin thermal clearance, plethysmographic wave amplitude, HR, MABP and skin temperature were 0.40±0.02 w · m^–1 C^–1, 9±1 mm, 98±5 beats · min^–1, 12.50±0.93 kPa and 33.3±3.4 C respectively. The minimal value of MABP was 9.58 ±1.06 kPa, whereas skin thermal clearance, plethysmographic wave amplitude, HR and skin temperature increased to 0.45±0.02 w · m^–1 C^–1, 29±3 mm, 110±4 beats · min^–1 and 34.4±0.4 C. Changes in skin thermal clearance correlated well with plethysmographic wave amplitude. Statistically significant changes in these two parameters occurred before significant change in HR, MABP or skin temperature. The results show that the new noninvasive probe using the thermal clearance method appears to be a useful device for measuring cutaneous microcirculation in anaesthetized humans, and responds more quickly than change in skin temperature, which is a delayed effect of skin blood flow change. Our results also show that the intensity of cutaneous vasodilatation induced by general anaesthesia did not relate to the vascular tone before anaesthesia.     

Different thermal dependency of cutaneous sympathetic outflow to glabrous and hairy skin in humans

We investigated the effects of ambient temperature on the sudomotor and vasoconstrictor components of skin sympathetic nerve activity (SSNA). The sympathetic traffic was measured by simultaneous microneurographic recording from post-ganglionic nerve fibres in the tibial and the peroneal nerves. When the ambient temperature was raised from 25° C to 34° C, both sudomotor and vasoconstrictor components of SSNA were enhanced in the peroneal nerve but were suppressed in the tibial nerve. The sudomotor and vasoconstrictor sympathetic outflows were elevated in both nerves when the temperature was lowered from 34° C to 18° C. Our results suggested that the sudomotor and the vasoconstrictor components of SSNA are differently modulated by ambient temperature. The difference in sudomotor and vasoconstrictor components of SSNA in the tibial and the peroneal nerves at different ambient temperature may have been responsible for the differences observed in sweating and vasoconstriction in glabrous and hairy skin.     

Effects of rhythmical muscle tension at 0.1 Hz on cardiovascular resonance and the baroreflex

This paper reports analysis of data from a previous study examining cardiovascular effects of rhythmical skeletal muscle tension (RSMT) at 0.1 Hz. Our analysis examined whether 0.1 Hz RSMT stimulates resonance properties of the cardiovascular system provided by baroreflex (BR) activity. Thirty-seven study participants tensed their large skeletal muscles, with and without crossing their legs, for 3-min periods at a rate of six tension/relaxation cycles/min. Tensing periods were preceded and followed by 3-min rest periods. RSMT elicited high-amplitude 0.1 Hz oscillations in the cardiovascular system. We found increases in spectral power of ECG R-R interbeat interval (RRI), systolic blood pressure (SBP) and pulse transit time (PTT) at this frequency. The increases in SBP and PTT oscillations were greater than those in RRI. Only in SBP and PTT did total variability (standard deviation) increase. The phase angle between RRI and SBP oscillations was ∼45°. Although alpha low-frequency baroreflex gain was attenuated by RSMT, it was not significantly changed at 0.1 Hz, consistent with BR-induced resonance effects. Our results are consistent with previous observations that 0.1 Hz RSMT is effective in treating vasovagal reactions and indicate that the pathway is through resonance characteristics of the BR system. Implications for resonance applications for resonance in the sympathetically mediated vascular tone baroreflex closed loop are discussed.     

The effect of high- and low-frequency transcutaneous electrical nerve stimulation upon cutaneous blood flow and skin temperature in healthy subjects.

The reported non-analgesic effects of transcutaneous electrical nerve stimulation (TENS) include alterations to the local circulation; however, research in this area has produced equivocal findings. In the present study, the effect of low- (4 Hz) and high-frequency (110 Hz) TENS on forearm skin blood perfusion was assessed using laser Doppler flowmetry. The effect on skin temperature was also assessed using a skin thermistor. Thirty healthy human volunteers were recruited and randomly assigned to a control or one of the two treatment groups. TENS was applied to the skin overlying the median nerve under double-blind conditions for 15 min. Blood flow and skin temperature readings were recorded pre-TENS, during TENS application and continued for 15 min post-TENS application. Analysis of results showed significant increases in blood perfusion during the treatment period in the low-frequency group when compared to the other two groups (P = 0.0106; ANOVA). No significant changes in skin temperature were observed. The results of this study demonstrate that low-frequency TENS produces a local increase in cutaneous blood flow.     

Effects of raloxifene and hormone replacement therapy on forearm skin elasticity in postmenopausal women

Objectives

Hormone replacement therapy (HRT) increases skin elasticity in postmenopausal women. However, the effects of raloxifene, a selective estrogen receptor modulator (SERM), on skin degenerative changes in postmenopausal women remain unknown. We investigated whether raloxifene increases skin elasticity, similar to HRT, in postmenopausal women.

Methods

In a 12-month trial, 17 postmenopausal women (mean age, 66.4 ± 7.8 years) received continuous raloxifene treatment (60 mg/day), 19 women (56.2 ± 6.4 years) received continuous 17-β estradiol treatment using a patch (0.72 mg/2 days) plus cyclic medroxyprogesterone acetate (2.5 mg/day, for 12 days/month), and 11 women (58.1 ± 7.3 years) did not receive either therapy. In each subject, the skin elasticity of the forearm was measured using a suction device at baseline and at 12 months after the start of the study.

Results

Raloxifene and HRT significantly increased skin elasticity from 52.4 ± 3.8% and 64.1 ± 7.2% at baseline to 55.1 ± 4.7% and 67.4 ± 7.4% after 12 months, respectively (P < 0.05, each), but the untreated subjects did not exhibit any significant change in skin elasticity during the study. The delta value for skin elasticity was significantly higher among the raloxifene and HRT subjects than among the untreated subjects (P < 0.05, each).

Conclusions

These findings suggest that raloxifene may have a beneficial effect on skin elasticity, which undergoes degenerative changes in postmenopausal women, in addition to its effects on bone metabolism.     

Experimental studies on the effects of vibration and noise on sympathetic nerve activity in skin

Summary Multi-unit sympathetic activity was recorded at elbow level from median nerve fascicles supplying glabrous skin of the left hand in five healthy subjects. The resultant vasomotor responses accompanying the neural activity were monitored by simultaneous recordings of skin blood flow using the laser doppler method and skin temperature in the innervation zones. No significant change in sympathetic activity was observed during handgrip exercise of the right hand under a constant gripping force of 2 kg. Subjects maintained the same gripping force of the right hand during exposure in random order to local vibration and/or noise, each type of exposure lasting 5 min with intervals of 20 min. A two-peaked significant increase in outflow from sympathetic nerves was observed during local exposure of the right hand to vibration with a frequency of 60 Hz and an acceleration of 50 m·s^–2, followed by a postexposure period which revealed a relative suppression of sympathetic nerve activity and a significant increase in blood flow. Noise at 100 dB(A) showed only an initial effect on skin sympathetic nerve activity (SSA), whereas when combined with local vibration at 60 Hz, a pronounced increase in neural activity was noticed, indicating a combined effect of vibration and noise. These results from direct recordings of SSA suggest a sympathetic vasomotor reflex mechanism triggered by local vibration stimuli to the hand.     

Effect of maximal arm exercise on skin blood flux in the paralyzed lower limbs in persons with spinal cord injury

 The purpose of the present study was to examine the effect of maximal arm exercise on the skin blood circulation of the paralyzed lower limbs in persons with spinal cord injury (PSCI). Eight male PSCI with complete lesions located between T3 and L1 performed graded maximal arm-cranking exercise (MACE) to exhaustion. The skin blood flux at the thigh (SBFT) and that at the calf (SBFC) were monitored using laser-Doppler flowmeter at rest and for 15 s immediately after the MACE. The subject's mean peak oxygen uptake and peak heart rate was 1.41 ± 0.22 l · min^–1 and 171.6 ± 19.2 beats · min^–1, respectively. No PSCI showed any increase in either SBFT or SBFC after the MACE, when compared with the values at rest. These results suggest that the blood circulation of the skin in the paralyzed lower limbs in PSCI is unaffected by the MACE. Accepted: 12 September 1996     

SSVEP and ERP measurement of cognitive fatigue caused by stereoscopic 3D

Characteristically within the resting brain there are slow fluctuations (around 0.1 Hz) of EEG and NIRS-(de)oxyhemoglobin ([deoxy-Hb], [oxy-Hb]) signals. An interesting question is whether such slow oscillations can be related to the intention to perform a motor act. To obtain an answer we analyzed continuous blood pressure (BP), heart rate (HR), prefrontal [oxy-Hb], [deoxy-Hb] and EEG signals over sensorimotor areas in 10 healthy subjects during 5 min of rest and during 10 min of voluntary finger movements. Analyses of prefrontal [oxy-Hb]/[deoxy-Hb] oscillations around 0.1 Hz and central EEG band power changes in the beta (alpha) band revealed that the positive [oxy-Hb] peaks preceded the central EEG beta (alpha) power peak by 3.6 ± 0.9 s in the majority of subjects. A similar relationship between prefrontal [oxy-Hb] and central EEG beta power was found during voluntary movements whereby the post movement beta power increase (beta rebound) is known to coexist with a decreased excitability of cortico-spinal neurons. Therefore, we speculate that the beta power increase ∼3 s after slow fluctuating [oxy-Hb] peaks during rest is indicative for a slow excitability change of central motor cortex neurons. This work provides the first evidence that initiation of finger movements at free will in relatively constant intervals around 10 s could be temporally related to slow oscillations of prefrontal [oxy-Hb] and autonomic blood pressure in the resting brain.     

Cardiovascular responses after brisk finger movement and their dependency on the “eigenfrequency” of the baroreflex loop

The baroreflex is mainly involved in short-term blood pressure regulation and strongly influenced by activations of medullary circulation centres in the brain stem and higher brain centres. One important feature of the baroreflex is its strong preference for oscillations around 0.1 Hz, which can be seen as resonance or “eigenfrequency” (EF) of the control loop (so-called Mayer waves). In the present study we investigated beat-to-beat heart rate intervals (RRI) and arterial blood pressure (BP) changes after brisk finger movement and their relationship to the “eigenfrequency” determined by cross spectral analysis between RRI and arterial blood pressure time series of 17 healthy subjects. The analyses revealed significant correlations between BP response magnitude (r = 0.63, p < 0.01) respectively RRI response magnitude (r = 0.59, p < 0.05) and EF. This can be interpreted in such a way that subjects with a “high” EF (>0.10 Hz) elicit larger BP responses as well as larger RRI responses when compared to subjects with a “low” EF (<0.10 Hz).     

Spinal TRPA1 ion channels contribute to cutaneous neurogenic inflammation in the rat

In the spinal dorsal horn, TRPA1 ion channels on central terminals of peptidergic primary afferent nerve fibers regulate transmission to glutamatergic and GABAergic interneurons. Here we determine the cutaneous anti-inflammatory effect of a spinally administered TRPA1 channel antagonist to test the hypothesis that spinal TRPA1 channels contribute to cutaneous neurogenic inflammation induced by sustained noxious stimulation. According to the hypothesis, spinal TRPA1 channels facilitate transmission of injury discharge to GABAergic interneurons that induce a dorsal root reflex, which results in increased release of proinflammatory compounds in the skin. Intraplantar capsaicin, a TRPV1 channel agonist, was used to induce neurogenic inflammation in anesthetized rats that were pretreated intrathecally (i.t.), intraplantarly (i.pl.) or intraperitoneally (i.p.) with vehicle or Chembridge-5861526 (CHEM, a TRPA1 channel antagonist). For assessment of neurogenic inflammation, the capsaicin-induced increase of cutaneous blood flow was determined adjacent to the capsaicin-treated skin site with a laser Doppler flowmeter. Capsaicin-induced a marked increase in cutaneous blood flow. The capsaicin-induced blood flow increase was attenuated in a dose-related fashion by i.t. pretreatment with CHEM (3-10 μg). Pretreatment with CHEM at a dose of 3 mg/kg i.p. or 20 μg i.pl. failed to attenuate the capsaicin-induced increase of blood flow. The results indicate that spinal TRPA1 channels contribute to cutaneous neurogenic inflammation adjacent to the injury site, probably by facilitating a dorsal root reflex in peptidergic primary afferent nerve fibers.     

Effects of exercise training and detraining on cutaneous microvascular function in man: the regulatory role of endothelium-dependent dilation in skin vasculature

This study investigated how exercise training and detraining affect the cutaneous microvascular function and the regulatory role of endothelium-dependent dilation in skin vasculature. Ten healthy sedentary subjects cycled on an ergometer at 50% of maximal oxygen uptake (O_2max) for 30 min daily, 5 days a week, for 8 weeks, and then detrained for 8 weeks. Plasma nitric oxide (NO) metabolites (nitrite plus nitrate) were measured by a microplate fluorometer. The cutaneous microvascular perfusion responses to six graded levels of iontophoretically applied 1% acetylcholine (ACh) and 1% sodium nitroprusside (SNP) in the forearm skin were determined by laser Doppler. After training, (1) resting heart rate and blood pressure were reduced, whereas O_2max, skin blood flow and cutaneous vascular conductance to acute exercise were enhanced; (2) plasma NO metabolite levels and ACh-induced cutaneous perfusion were increased; (3) skin vascular responses to SNP did not change significantly. However, detraining reversed these effects on cutaneous microvascular function and plasma NO metabolite levels. The results suggest that endothelium-dependent dilation in skin vasculature is enhanced by moderate exercise training and reversed to the pretraining state with detraining.