Decrease In Skin Blood Flow Research Articles

Nicotine exacerbates exertional heat strain in trained men: a randomized, placebo-controlled, double-blind study.

To determine whether using nicotine exacerbates exertional heat strain through an increased metabolic heat production (Hprod) or decreased skin blood flow (SkBF), 10 nicotine-naïve trained males [37 ± 12 yr; peak oxygen consumption (V̇o2peak): 66 ± 10 mL·min-1·kg-1] completed four trials at 20°C and 30°C following overnight transdermal nicotine (7 mg·24 h-1) and placebo use in a crossover, double-blind design. They cycled for 60 min (55% V̇o2peak) followed by a time trial (∼75% V̇o2peak) during which measures of gastrointestinal (Tgi) and mean weighted skin ([Formula: see text]sk) temperatures, SkBF, Hprod, and mean arterial pressure (MAP) were made. The difference in ΔTgi between nicotine and placebo trials was greater during 30°C (0.4 ± 0.5°C) than 20°C (0.1 ± 0.7°C), with [Formula: see text]sk higher during nicotine than placebo trials (0.5 ± 0.5°C, P = 0.02). SkBF became progressively lower during nicotine than placebo trials (P = 0.01) and progressively higher during 30°C than 20°C trials (P < 0.01); MAP increased from baseline (P < 0.01) and remained elevated in all trials. The difference in Hprod between 30°C and 20°C trials was lower during nicotine than placebo (P = 0.01) and became progressively higher during 30°C than 20°C trials with exercise duration (P = 0.03). Mean power output during the time trial was lower during 30°C than 20°C trials (24 ± 25 W, P = 0.02), and although no effect of nicotine was observed (P > 0.59), two participants (20%) were unable to complete their 30°C nicotine trials as one reached the ethical limit for Tgi (40.0°C), whereas the other withdrew due to "nausea and chills" (Tgi = 39.7°C). These results demonstrate that nicotine use increases thermal strain and risk of exertional heat exhaustion by reducing SkBF.NEW & NOTEWORTHY In naïve participants, acute nicotine use exerts a hyperthermic effect that increases the risk of heat exhaustion during exertional heat strain, which is driven by a blunted skin blood flow response. This has implications for 1) populations that face exertional heat strain and demonstrate high nicotine use (e.g., athletes and military, 25%-50%) and 2) study design whereby screening and exclusion for nicotine use or standardization of prior use (e.g., overnight abstinence) is encouraged.

Routine skincare - What I advise to defy aging?

Aging is a natural process and a fact of life, but increasing life expectancy and the desire to look young have led to seeking out answers concerning skincare to defy aging. Various reasons for aging have been implicated such as the effect of gravity on soft tissue results in their sagging over the facial skeleton, sun damage, hormonal changes, decreased skin blood flow, weight gain, fascial and ligament laxity, shrinkage of glandular tissue, and skeletal resorption. Although intrinsic aging is genetically driven, extrinsic aging is affected by sun exposure, environmental insults, stress, sleep patterns, smoking, and various lifestyle factors. Extrinsic aging can be delayed or reduced by various lifestyle modifications such as moving naturally throughout the day, mindful eating, good sleep, prioritizing stress relief, strong social network with family and friends, and a good skincare routine. Good skin health reflects overall well-being. A good skincare routine of gentle cleansing, moisturizing, and sun-screening along with a healthy lifestyle can help reduce aging changes.

Enhanced Contraction of Arterial Smooth Muscle Cell in Skin Artery Is Sensitive to Hyperpolarization Mediated by BKCa Channel in Chronic Constriction Injury Model Rat.

Previous our study found that improvement of skin blood flow associated with neuropathic pain using vasodilators is useful for alleviation of neuropathic pain. In this study, we aimed to elucidate the mechanism underlying enhanced vasorelaxation induced by vasodilators, which increase cAMP and cyclic guanosine monophosphate (cGMP), in chronic constriction injury model rat. We assessed vasorelaxation effect of vasodilators by measurement of isometric contraction in isolated plantar artery from chronic constriction injury of sciatic nerve model rats. Nifedipine, a voltage-dependent Ca2+ channel inhibitor, NS1619, Ca2+-activated K+ (BKCa) channel opener, and diazoxide, an ATP-sensitive potassium channel opener, -induced vasorelaxation in ipsilateral plantar artery was enhanced compared to the these in contralateral plantar artery. Sodium nitroprusside (SNP), a nitric oxide (NO) donor, and substance P, a NK1 receptor agonist, caused vasorelaxation in both ipsilateral and contralateral artery. The vasorelaxation induced by SNP and substance P in ipsilateral artery is enhanced compared to the these in contralateral artery. Isoprenaline, a β adrenoceptor agonist, and salbutamol, a β2 adrenoceptor agonist, caused strong vasorelaxation in ipsilateral artery but not in contralateral artery. Iberiotoxin, a BKCa channel inhibitor, prominently suppressed the enhanced vasorelaxation induced by SNP, substance P, isoprenaline and salbutamol. In summary, the enhanced contraction of arterial smooth muscle cell in skin artery is sensitive to hyperpolarization in chronic constriction injury model rat. Furthermore, β adrenoceptor agonist would be a good drug to improve the decreased skin blood flow because it has selective vasorelaxation to ipsilateral plantar artery.

AW-NI-6: MINERALOCORTICOID RECEPTOR ACTIVATION LEADS TO HIGH BLOOD PRESSURE DUE TO BODY POTASSIUM AND WATER LOSS

Objective: Mineralocorticoid receptor (MR) activation is known to reduce renal Na+ elimination and increase body fluid, resulting in arterial hypertension. We have reported earlier that high salt intake, chronic renal failure and psoriasis occur blood pressure increases initiated by body water loss. Here we tested the hypothesis that DOCA treatment induces a similar adaptive water conservation response that also causes arterial hypertension. Design and method: Male C57BL/6J mice on the low-salt diet (&lt;0.1% NaCl) were divided into four groups: tap water (control), tap water with subcutaneous 25 mg DOCA (DOCA), 1% NaCl water with DOCA (DOCA salt), 1.44% NaHCO3 water with DOCA (DOCA NaBic). We performed continuous metabolic cage studies. Na+, K+, and water were measured in mice tissue by desiccation and consecutive dry ashing. Blood pressure was measured by telemetry. We also studied body composition, glucocorticoid-receptor (GR) protein/chromatin interaction, skin blood flow perfusion and renal vascular resistance. Metabolome and key enzyme activities of energy production in kidney, skeletal muscle and in liver were compared between four groups. Results: Compared to control mice, DOCA mice showed increased urine volume, lower urine osmolality and increased blood pressure. DOCA salt developed arterial hypertension within 3 days of the experiment (P &lt; 0.001, Fig. 1A). In DOCA salt mice, K+ and water loss occurs in the initiation phase of arterial hypertension (Fig. 1B), indicating solute and water loss from the intracellular space. Further water loss was then prevented by secondary Na+ accumulation, indicating that the initial MR-driven dehydration reverted back to normal body fluid level by means of Na+ accumulation. Additional physiological adaptation to DOCA salt-driven body water loss included increased vascular resistance (Fig. 1C) and catabolic amino acid breakdown (Fig. 1D). DOCA NaBic mice showed similar massive primary K+ loss and secondary Na+ retention, but no arterial hypertension occurred (Fig. 1A). While DOCA salt decreased skin blood flow, DOCA NaBic increased it (Fig. 1C). DOCA salt mice showed renal glutamine catabolism as well as muscle protein catabolism (Fig. 1D). This catabolic state was coupled with glucocorticoid receptor binding in skeletal muscle. Conclusions: DOCA salt leads to pronounced initial K+ and water loss with hypertension. Na+ retention occurs only secondarily and is a compensatory response that reverts initial body water loss back to normal body water levels. Additional NaBic feeding reveals that the blood pressure level in mice with MR activation is determined by changes in blood flow independent of body Na+ or water content.

Nexus Between Human Thermoregulation and Cardiovascular Functions—A Preliminary Simulation for a Moderate Variation of Temperature

AbstractThough the interaction between cardiovascular functions and thermoregulation is enormously complex yet immensely important, very little effort to date has been spent to simulate it from a system point of view. The present work aims at simulating the mutual interaction of human thermoregulation and cardiovascular functions by combining simple models of these two systems. While for thermoregulation, a lumped parameter multi-node model has been developed, a SIMULINK-based approach of electrical analogy has been taken for the cardiovascular system. These two models are coupled by different physiological and control actions, represented by well-established correlations. Three case studies have been conducted. In the first case, thermoregulation of a healthy human being is considered for a prescribed temperature cycle of moderate variation. Under heat stress, cardiac output increases by a joint effect of heart rate and stroke volume while under the cold condition, the variation of the cardiac output is less and is primarily governed by the heart rate. For the case of a reduced ejection fraction of the left ventricle, though there is a notable decrease in skin blood flow, negligible variation in skin and core temperature is observed. In the case of acute aortic stenosis, it is found that the blood pressure falls severely from its normal level causing hypotension and is further aggravated even under moderate heat stress. Such a situation might have further consequences like heat stroke. Finally, the limitations of the present study have been highlighted and suggestions have been made for further improvement.

Cold-induced vasodilation in abstinent smokers with and without a 12-hour nicotine patch.

This study was designed to identify the effects of a 12-h nicotine patch administration on cold induced vasodilation (CIVD) in healthy young chronic smokers following 16 h of abstinence from smoking. Two laser Doppler probes and temperature thermocouples were placed on the dorsal part of the distal phalanx of the middle and ring fingers of 7 smokers (>12 cigarettes/day). Following 16 h of abstinence from smoking, smokers were tested with and without administration of a 21mg transdermal nicotine patch (NicoDerm® ). Each participant's right hand was immersed in cold (~5°C) water for 40 min. Cutaneous vascular conductance (CVC) was calculated from non-invasive arterial finger blood pressure and skin blood flow and expressed as a percentage of peak CVC observed during hand skin heating to 44°C. For comparison purposes, the CIVD response of a non-smoking cohort without nicotine patch (n = 10) was also examined. Baseline CVC was similar in smokers and non-smokers (27.8 ± 12.6 CVC % peak). The initial vasoconstriction during cold-water immersion decreased skin blood flow to 4.0 ± 3.9 CVC % peak in both smokers and non-smokers. The onset of CIVD in smokers (4.5 ± 1.5 min) was delayed compared to non-smoker (3.3 ± 0.8 min, p < .05). The area under the CVC %peak-time curve during cold-water immersion averaged 1250 ± 388 CVC %peak · min in non-smokers which was larger (p < .05) than smokers with or without nicotine (789 ± 542 and 862 ± 517 CVC %peak · min, respectively). Chronic smoking impaired the CIVD response to cold-water immersion of the hand; however, the impaired CIVD response in 16 h of abstinence from smoking was not influenced by application of a 21mg transdermal nicotine patch.

Peripheral Blood Flow Changes to Cutaneous and Muscular Beds in Response to Acute Hookah Smoking

Hookah (waterpipe) smoking is a growing tobacco epidemic. Though perceived as a safer tobacco alternative, hookah smoke contains, in addition to tobacco combustion products, large amounts of charcoal combustion products-implicated in cardiovascular disease-from the burning charcoal used to heat the flavored tobacco. To date, little is known on the vascular effects of hookah smoking. The aim of this study was to characterize the peripheral circulatory response to acute hookah smoking in cutaneous and muscular beds. In 21 healthy young adult habitual hookah smokers who did not smoke cigarettes (age 24 ± 1 years, mean ± SE), we measured plasma nicotine, exhaled carbon monoxide, skin blood flow (laser Doppler velocimetry) and calf muscle blood flow (strain-gauge plethysmography) before and for up to 60 minutes after ad lib hookah smoking. In nine subjects, nonsmoking time-control studies were performed. Hookah smoking, which increased plasma nicotine by 5.8 ng/ml (from 0.6 ± 0.1 to 6.4 ± 1.3, p <0.001) and exhaled carbon monoxide by 27 ppm (from 2.7 ± 0.2 to 29.5 ± 2.2, p <0.001), decreased skin blood flow by 23% (20.1 ± 2.8 to 14.8 ± 1.9 units, p <0.001) and increased skeletal muscle blood flow by 34% (2.3 ± 0.1 to 2.9 ± 0.2 units, p = 0.010). These responses required more than one hour to recover after smoking cessation. All cardiovascular parameters were unchanged in the nonsmoking time-control studies. Although perceived to be innocuous, hookah smoking produces acute cutaneous vasoconstriction with skeletal muscle vasodilation, a dissociated pattern of peripheral blood flow responses that is characteristic of nicotine and carbon monoxide. In conclusion, these findings provide objective evidence to challenge the perception that hookah smoking is a safer tobacco alternative.

Changes in skin blood flow, respiration and blood pressure in participants reporting motion sickness during sinusoidal galvanic vestibular stimulation.

What is the central question of the study? We have previously shown that sinusoidal galvanic vestibular stimulation induces greater modulation of skin sympathetic nerve activity, but not muscle sympathetic nerve activity, in participants who report nausea during simulated motion, but the effects on skin blood flow and blood pressure are unknown. What is the main finding and its importance? During vestibular stimulation, nausea was associated with a greater increase in skin blood flow and a progressive reduction in skin sympathetic nerve activity, but no changes in muscle sympathetic nerve activity. This emphasizes the differential changes in sympathetic outflow to different tissues during nausea. We tested the hypothesis that galvanic vestibular stimulation, which produces illusions of side-to-side swaying, causes a greater reduction in skin blood flow in participants who report stimulation-induced nausea. A retrospective analysis was performed on data obtained in 30participants. Bipolar sinusoidal galvanic vestibular stimulation (sGVS) was applied across the mastoid processes (±2mA, 0.08Hz) for 21min. ECG, continuous blood pressure, respiration and skin blood flow were recorded. Muscle sympathetic nerve activity was recorded in 17 participants and skin sympathetic nerve activity in 12. Ten participants reported motion sickness, whereas 20 did not. Both groups showed an initial reduction in skin (finger) blood flow during sGVS, followed by a sustained increase and a subsequent return towards baseline levels throughout the stimulation; the increase was greater in those who experienced nausea. The increase fits with the progressive reduction in skin sympathetic nerve activity observed in the nauseous group. Mean blood pressure was significantly lower in those who experienced nausea and showed a much larger increase at the onset of sGVS, compared with those who did not. Moreover, the respiratory rate was higher at the outset for the subjects who experienced nausea, decreasing progressively during sGVS, whereas respiratory rate remained constant in those who did not experience nausea. Heart rate was more labile in the subjects who experienced nausea, showing a sustained increase towards the end of stimulation. We have shown that several autonomic parameters change during the nausea induced by vestibular stimulation, but a sustained decrease in skin blood flow is not a hallmark of incipient motion sickness.

Application of Ice for Postoperative Total Knee Incisions - Does this Make Sense? A Pilot Evaluation of Blood Flow Using Fluorescence Angiography.

IntroductionTotal knee arthroplasty (TKA) is a common procedure with significant advances over the past several years, many pertaining to improved perioperative pain control. Cryotherapy is one method thought to decrease swelling and pain postoperatively. To our knowledge no study has directly visualized the effect cryotherapy has on skin blood flow following TKA. The primary aim was to determine if cryotherapy (icing) affects peri-incisional skin blood flow and if this is lessened with an alternate placement of the ice. We hypothesized that blood flow would decrease following cryotherapy, and this decrease would be greater with ice placed directly over the incision as compared to placement along the posterior knee.MethodsThis study included 10 patients who underwent TKA. During the postoperative hospitalization, they were given an injection of indocyanine green dye. A baseline image was recorded of the skin blood flow. Images were then collected following a five-minute interval placement of ice over the incision. The experiment was then repeated with the ice placed along the posterior knee. ResultsThere was an approximate 40% decrease in skin blood flow following placement of the ice compared to baseline. We observed a greater decrease in blood flow when ice was placed over the incision as compared to when ice was placed posterior to the knee (p ≤ 0.020).ConclusionWe found a significant decrease in peri-incisional blood flow with icing of the knee. Physicians should be cognizant of this when recommending cryotherapy to patients after surgery, especially in at-risk wounds.

Cold-induced cutaneous vasoconstriction in humans: Function, dysfunction and the distinctly counterproductive.

What is the topic of this review? This review presents an update and synthesis of normal mechanisms of human cutaneous vasoconstriction in response to cold stress. It then discusses conditions in which cutaneous vasoconstrictor responses are excessive or insufficient and cases in which cold-induced vasoconstrictor responses become counter to maintaining thermal and haemodynamic homeostasis. What advances does it highlight? The review highlights our current understanding of the mechanisms that mediate alterations in cold-induced cutaneous vasoconstriction in pathology and environmental extremes, which has important clinical implications for preventing cold- and cardiovascular-related deaths. In humans, cold-induced peripheral vasoconstriction is an essential element of body temperature regulation. Given that the thermoregulatory system responds rapidly to changes in skin temperature, sympathetically mediated cutaneous vasoconstriction represents a crucial 'first line of defense' against excessive reduction in body temperature. Sympathetic noradrenergic vasoconstrictor nerves cause a rapid decrease in skin blood flow, thus increasing the insulative capacity of the skin and decreasing heat loss from the body. Small changes in the activity of these nerves are also responsible for the subtle changes in skin blood flow that occur with normal daily activities or minor changes in environmental temperature. With ageing, hypertension and other conditions, the cutaneous reflex vasoconstrictor response can become excessive or insufficient. Healthy older adults have impaired reflex vasoconstriction, which may result in an impaired ability to defend body temperature in some circumstances. Hypertension is associated with augmented vasoconstriction, which could have pathological implications for left ventricular afterload in individuals already at risk for cardiovascular events. Finally, in some cases, the reflex vasoconstrictor response becomes distinctly counterproductive to its own goals of maintaining cardiovascular and thermoregulatory homeostasis. Examples include Raynaud's phenomenon, in which exaggerated vasoconstriction can produce ischaemia in the periphery, and the cutaneous vasoconstrictor response to therapeutic body cooling in severe hyperthermia, which can limit the heat exchange necessary to prevent serious heat illness.

Glabrous and non-glabrous vascular responses to mild hypothermia

This study examined cutaneous vasoconstriction to whole-body hypothermia, specifically contributions of neural and endothelial vasomotor responses in glabrous and non-glabrous skin. Eleven participants were semi-recumbent at an ambient temperature of 22 °C for 30 min, after which ambient temperature was decreased to 0 °C until rectal temperature (Tre) had decreased by 0.5 °C. Laser-Doppler fluxmetry was measured at the forehead and thigh for measures of glabrous and non-glabrous skin, respectively; wavelet analysis was performed on the laser-Doppler signal to determine endothelial and neural activities. Hypothermia took on average 97 ± 7 min and caused marked decreases at glabrous (42 ± 5%baseline, p < 0.001) and non-glabrous (69 ± 4%baseline, p < 0.001) skin. In glabrous skin, neural activity increased from 11 ± 1% at thermoneutral to 18 ± 1% (p < 0.001). In non-glabrous skin there was an initial decrease (p = 0.001) in neural activity from 13 ± 2% to 9 ± 1% (−0.2 °C decrease in Tre) and then increased (p = 0.002) to 21 ± 2% baseline at −0.5 °C Tre. Endothelial activity decreased in both glabrous (16 ± 3% to 6 ± 1%, p < 0.001) and non-glabrous (15 ± 1% to 7 ± 1%, p = 0.003) skin. Hypothermia elicits large decreases in skin blood flow in both glabrous and non-glabrous skin that are related to increases in neural activity and a reduction of endothelial activity.

Body temperature, cutaneous heat loss and skin blood flow during epidural anaesthesia for emergency caesarean section.

It is not clear how converting epidural analgesia for labour to epidural anaesthesia for emergency caesarean section affects either cutaneous vasomotor tone or mean body temperature. We hypothesised that topping up a labour epidural blocks active cutaneous vasodilation (cutaneous heat loss and skin blood flow decrease), and that as a result mean body temperature increases. Twenty women in established labour had body temperature, cutaneous heat loss and skin blood flow recorded before and after epidural top-up for emergency caesarean section. Changes over time were analysed with repeated measures ANOVA. Mean (SD) mean body temperature was 36.8 (0.5)°C at epidural top-up and 36.9 (0.6)°C at delivery. Between epidural top-up and delivery, the mean (SD) rate of increase in mean body temperature was 0.5 (0.5) °C.h-1 . Following epidural top-up, chest (p < 0.001) and forearm (p = 0.004) heat loss decreased, but head (p = 0.05), thigh (p = 0.79) and calf (p = 1.00) heat loss did not change. The mean (SD) decrease in heat loss was 15 (19) % (p < 0.001). Neither arm (p = 0.06) nor thigh (p = 0.10) skin blood flow changed following epidural top-up. Despite the lack of change in skin blood flow, the most plausible explanation for the reduction in heat loss and the increase in mean body temperature is blockade of active cutaneous vasodilation. It is possible that a similar mechanism is responsible for the hyperthermia associated with labour epidural analgesia.

Deactivation of the prefrontal cortex during exposure to pleasantly-charged emotional challenge

Our laboratory reported that facial skin blood flow may serve as a sensitive tool to assess an emotional status and that both prefrontal oxygenation (as index of regional cerebral blood flow) and facial skin blood flow decrease during positively-charged emotional stimulation, without changing hand skin blood flow and arterial pressure. However, the focal location of the prefrontal responses in concentration of oxygenated haemoglobin (Oxy-Hb) that correlate with peripheral autonomic reaction remained unknown. This study was undertaken using 22-channel near-infrared spectroscopy to reveal spatial distribution of the responses in Oxy-Hb within the prefrontal cortex (PFC) during emotionally-charged audiovisual stimulation. Pleasantly-charged (comedy) stimulation caused a substantial decrease of Oxy-Hb in all regions of the PFC in 18 subjects, especially in the rostroventral frontopolar PFC, whereas negatively-charged (horror) or neutral stimulation (landscape) exhibited a weaker decrease or insignificant change in the prefrontal Oxy-Hb. In the rostral parts of the dorsolateral and ventral frontopolar PFC, the oxygenation response during comedy stimulation exhibited the most significant positive correlation with the decrease in facial skin blood flow. Thus the rostral regions of the PFC play a role in recognition and regulation of positive emotion and may be linked with neurally-mediated vasoconstriction of facial skin blood vessels.

Early and Late Cardiovascular and Metabolic Responses to Mixed Wine: Effect of Drink Temperature.

Aim: Red wine is usually ingested as an unmixed drink. However, mixtures of wine with juices and/or sucrose (mixed wine) are becoming more and more popular and could be ingested at either cold or hot temperature. Although the temperature effects on the cardiovascular system have been described for water and tea, with greater energy expenditure (EE) and lower cardiac workload with a colder drink, little information is available on the impact of temperature of alcoholic beverages on alcoholemia and cardiometabolic parameters. The purpose of the present study was to compare the acute cardiovascular and metabolic changes in response to mixed wine ingested at a cold or at a hot temperature.Methods: In a randomized crossover design, 14 healthy young adults (seven men and seven women) were assigned to cold or hot mixed wine ingestion. Continuous cardiovascular, metabolic, and cutaneous monitoring was performed in a comfortable sitting position during a 30-min baseline and for 120 min after ingesting 400 ml of mixed wine, with the alcohol content adjusted to provide 0.4 g ethanol/kg of body weight and drunk at either cold (3°C) or hot (55°C) temperature. Breath alcohol concentration was measured intermittently throughout the study.Results: Overall, alcoholemia was not altered by drink temperature, with a tendency toward greater values in women compared to men. Early responses to mixed wine ingestion (0–20 min) indicated that cold drink transiently increased mean blood pressure (BP), cardiac vagal tone, and decreased skin blood flow (SkBf) whereas hot drink did not change BP, decreased vagal tone, and increased SkBf. Both cold and hot mixed wine led to increases in EE and reductions in respiratory quotient. Late responses (60–120 min) led to similar cardiovascular and metabolic changes at both drink temperatures.Conclusion: The magnitude and/or the directional change of most of the study variables differed during the first 20 min following ingestion and may be related to drink temperature. By contrast, late changes in cardiometabolic outcomes were similar between cold and hot wine ingestion, underlying the typical effect of alcohol and sugar intake on the cardiovascular system.

Effect of reflex and mechanical decreases in skin blood flow on exogenous cholinergic‐induced eccrine sweating in humans

Human skin blood flow (SkBF) and sweating increase concurrently during increases in skin sympathetic nerve activity and subsequent neurotransmitter release to these cutaneous appendages. Previous studies have blocked sweating without affecting SkBF with the use of the muscarinic agonist atropine, but few have altered SkBF without affecting sweating because standard methods such as introducing an α‐adrenergic agonist decrease SkBF but also can engage eccrine sweat gland receptors. Thus, this study aimed to utilize non‐adrenergic mechanical perturbations to decrease SkBF during intradermal perfusion of a cholinergic agonist. Three intradermal microdialysis fibers were placed in dorsal forearm skin of 4 women and 3 men (age 24±1 yr, height 173±4 cm, weight 80±8 kg) to perfuse 2 doses of pilocarpine nitrate (0.01 and 1.66 mg/ml, corresponding to the ED50 and EMAX from previous dose‐response modeling) or the vehicle (lactated Ringer's). Forearm SkBF (laser‐Doppler flowmetry) was decreased for 3 min by engaging the venoarteriolar response (arm lowered ~30 cm from heart level; CVAR), venoarteriolar response plus decreased perfusion pressure (venous occlusion by proximal cuff inflation; CVAR with ΔPP), and ischemia (arterial occlusion by proximal cuff inflation); sweat rate was measured by perfusing anhydrous medical air through a ventilated capsule (capacitance hygrometry). Drug infusions significantly increased SkBF (+87±18 and +57±16 units) and sweating (+0.37±0.20 and +0.64±0.15 mg/ml/min, for pilocarpine ED50 and EMAX, respectively) compared to vehicle control in which SkBF minimally increased (+8±4 units) and there was no alteration in sweating (−0.02±0.09). Decreased SkBF was observed with CVAR (−26±14, −33±9, and −38±9%), CVAR with ΔPP (−62±7, −42±20 and −61±8%), and ischemia (−99±1, −92±5 and −93±2% for pilocarpine ED50, pilocarpine EMAX, and vehicle control, respectively). Despite these significant decreases in SkBF, changes in eccrine sweat rate were minimal (CVAR = −1±12, +3±3, and −2±5%; CVAR with ΔPP = +3±7, −2±4, and −3±4%; and ischemia = +5±10, +5±5, and +6±5% for pilocarpine ED50, pilocarpine EMAX, and vehicle control, respectively). These data suggest that very acute decreases in SkBF do not proportionally decrease cholinergic‐induced sweating in human forearm skin.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Effect of decreasing peripheral skin blood flow via local axon reflexes, decreases in perfusion pressure, and ischemia during systemic thermal‐induced eccrine sweating in humans

In humans, skin blood flow (SkBF) and sweating are tightly coupled, suggesting common neural control and regulation and possible interactive effects of extracellular fluid delivery and sweat secretion. This study was designed to separate these two sympathetic nervous system end‐organ responses via SkBF‐decreasing mechanical perturbations in the presence of a strong sudomotor drive. Two women and 4 men (age 26±1 yrs and BMI 24±4 kg/m2) were tested in normothermia and heat stress conditions, by pumping neutral (34°C) and hot (46–50°C) water through a high‐density tube‐lined suit to either maintain internal temperature (pill telemetry) or increase it by ~1.0°C. Arm and leg SkBF (laser‐Doppler flowmetry) was decreased for 3 min by engaging the venoarteriolar response (limb lowered ~30 cm from heart level; CVAR), venoarteriolar response plus a decrease in perfusion pressure (venous occlusion by proximal cuff inflation; CVAR with ΔPP), and ischemia (arterial occlusion by proximal cuff inflation). Decreased SkBF was observed with CVAR (30±7 and 60±15%), CVAR with ΔPP (44±12 and 86±11%), and ischemia (96±1 and 99±1% for the arm and leg, respectively) during normothermia. Despite these significant decreases in SkBF, there were no significant effects on transepidermal water loss (TEWL). Heat stress increased intestinal temperature from 37.1±0.1 to 38.0±0.1°C, heart rate (ECG) from 65±5 to 93±4 bpm, arm cutaneous vascular conductance (SkBF/mean arterial pressure*100) from 52±12 to 473±85 units, and forearm sweat rate (capacitance hygrometry) from 0.0 to 0.6±0.1 mg/ml/min. During heat stress, decreased SkBF was also observed during CVAR (20±7 and 17±6%), CVAR with ΔPP (39±9 and 52±13%), and ischemia (99±1 and 100±1% for the arm and leg, respectively). Despite these significant decreases in SkBF, eccrine sweat rate was not significantly affected. These data indicate that a wide range of acute changes in SkBF do not appear to affect TEWL or eccrine sweating in peripheral skin.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

TRPA1 sensitization during diabetic vascular impairment contributes to cold hypersensitivity in a mouse model of painful diabetic peripheral neuropathy.

BackgroundDiabetic peripheral neuropathy is a common long-term complication of diabetes. Accumulating evidence suggests that vascular impairment plays important roles in the pathogenesis of diabetic peripheral neuropathy, while the mechanism remains unclear. We recently reported that transient receptor potential ankyrin 1 (TRPA1) is sensitized by hypoxia, which can contribute to cold hypersensitivity. In this study, we investigated the involvement of TRPA1 and vascular impairment in painful diabetic peripheral neuropathy using streptozotocin-induced diabetic model mice.ResultsStreptozotocin-induced diabetic model mice showed mechanical and cold hypersensitivity with a peak at two weeks after the streptozotocin administration, which were likely to be paralleled with the decrease in the skin blood flow of the hindpaw. Streptozotocin-induced cold hypersensitivity was significantly inhibited by an antagonist HC-030031 (100 mg/kg) or deficiency for TRPA1, whereas mechanical hypersensitivity was unaltered. Consistent with these results, the nocifensive behaviors evoked by an intraplantar injection of the TRPA1 agonist allyl isothiocyanate (AITC) were enhanced two weeks after the streptozotocin administration. Both streptozotocin-induced cold hypersensitivity and the enhanced AITC-evoked nocifensive behaviors were significantly inhibited by a vasodilator, tadalafil (10 mg/kg), with recovery of the decreased skin blood flow. Similarly, in a mouse model of hindlimb ischemia induced by the ligation of the external iliac artery, AITC-evoked nocifensive behaviors were significantly enhanced three and seven days after the ischemic operation, whereas mechanical hypersensitivity was unaltered in TRPA1-knockout mice. However, no difference was observed between wild-type and TRPA1-knockout mice in the hyposensitivity for current or mechanical stimulation or the deceased density of intraepidermal nerve fibers eight weeks after the streptozotocin administration.ConclusionThese results suggest that TRPA1 sensitization during diabetic vascular impairment causes cold, but not mechanical, hypersensitivity in the early painful phase of diabetic peripheral neuropathy. However, TRPA1 may play little or no role in the progression of diabetic peripheral neuropathy.

Effect of sympathetic nerve blockade on low‐frequency oscillations of forearm and leg skin blood flow in healthy humans

To Examine the effect of inhibiting sympathetic function on cutaneous vasomotion in the forearm and leg. Intradermal microdialysis fibers were placed in the forearm and leg, one as an untreated control (lactated Ringer's) and the other perfused with bretylium tosylate to block sympathetic nerves. Skin blood flow was monitored using laser Doppler flowmetry. Baseline was collected for 10 minutes before local skin temperature was increased to 42°C. Spectral analysis was performed using a Morlet wavelet. Bretylium tosylate increased skin blood flow during baseline in the forearm (d=1.6, P<.05) and leg (d=0.5, P<.05) and decreased skin blood flow at both sites during both the initial peak (d≥1.0, P<.05) and plateau (d≥0.8, P<.05). Treatment with bretylium tosylate reduced wavelet amplitude associated with neural activity during baseline in the forearm (d=1.6, P<.05) and leg (d=0.9, P<.05). This reduction in wavelet amplitude at bretylium tosylate-treated sites was also observed during the initial vasodilation to local heating in both the forearm (d=1.6, P<.05) and leg (d=1.4, P<.05) and during the sustained vasodilation in both the forearm (d=1.6, P<.05) and leg (d=1.2, P<.05). Our data support that the frequency band (0.021-0.052 Hz) associated with neurogenic activity appears to be correct having a large sympathetic component.

Autonomic dysreflexia: Somatosympathetic and viscerosympathetic vasoconstrictor responses to innocuous and noxious sensory stimulation below lesion in human spinal cord injury

Autonomic dysreflexia is a dangerous elevation in blood pressure in people with spinal cord injury (SCI), produced by a spinally-mediated reflex activation of sympathetic vasoconstrictor neurones supplying skeletal muscle and the gut. Current dogma states that, apart from visceral inputs - such as those originating from a distended bladder or impacted colon - autonomic dysreflexia is triggered by noxious inputs below the lesion. However, while selective stimulation of small-diameter afferents in muscle or skin evokes a sustained increase in muscle sympathetic nerve activity and blood pressure, and a transient increase in skin sympathetic nerve activity and decrease in skin blood flow in able-bodied subjects, such noxious inputs have no effects on blood pressure and skin blood flow in SCI individuals. Conversely, weak electrical stimulation over the abdominal wall, which in able-bodied subjects is not painful and activates large-diameter cutaneous afferents, causes a marked increase in blood pressure in SCI but not in able-bodied subjects. Moreover, vibration of the penis in spinal-injured men, which is not noxious, caused marked vasoconstriction and increases in blood pressure, similar to those produced by non-noxious distension of the bladder during urodynamics procedures. This suggests that activation of large-diameter somatic afferents, not small-diameter afferents, triggers the increases in vasoconstrictor drive that lead to autonomic dysreflexia, arguing against current dogma on the importance of noxious inputs in triggering autonomic dysreflexia.

Renal sympathetic nerve, blood flow, and epithelial transport responses to thermal stress.

Thermal stress is a profound sympathetic stress in humans; kidney responses involve altered renal sympathetic nerve activity (RSNA), renal blood flow, and renal epithelial transport. During mild cold stress, RSNA spectral power but not total activity is altered, renal blood flow is maintained or decreased, and epithelial transport is altered consistent with a sympathetic stress coupled with central volume loaded state. Hypothermia decreases RSNA, renal blood flow, and epithelial transport. During mild heat stress, RSNA is increased, renal blood flow is decreased, and epithelial transport is increased consistent with a sympathetic stress coupled with a central volume unloaded state. Hyperthermia extends these directional changes, until heat illness results. Because kidney responses are very difficult to study in humans in vivo, this review describes and qualitatively evaluates an in vivo human skin model of sympathetically regulated epithelial tissue compared to that of the nephron. This model utilizes skin responses to thermal stress, involving 1) increased skin sympathetic nerve activity (SSNA), decreased skin blood flow, and suppressed eccrine epithelial transport during cold stress; and 2) increased SSNA, skin blood flow, and eccrine epithelial transport during heat stress. This model appears to mimic aspects of the renal responses. Investigations of skin responses, which parallel certain renal responses, may aid understanding of epithelial-sympathetic nervous system interactions during cold and heat stress.