Skin Vasoconstriction Research Articles

The intersection-of-asymptotes method applied to the study of skin temperature changes over time during running exercise

The intersection of asymptotes method is used to describe the changes in skin temperature of the human body during running exercise. Skin temperature variations are induced by thermoregulatory mechanisms, which are influenced by both physiological and environmental factors. The aim of this study is to succinctly and comprehensively connect these factors to create an easily interpretable tool for understanding this process. Based on simplified energy balance equations under dynamic conditions for both the early and late stages of exercise, two asymptotic solutions for skin temperature are derived. The point of intersection between these solutions determines the moment at which the transition from skin vasoconstriction to vasodilation occurs. The shapes and the intersection of the two asymptotes enable the inference and interpretation of actual skin temperature variations throughout the course of exercise.

Comparisons of Evoked Skin Vasomotor and Sudomotor Responses to Single Pulse Median Nerve Stimulation

The sensorimotor dysfunction caused by cervical and thoracic spinal cord injury (SCI) is concomitant with sympathetic nervous system dysfunction, evidenced by the high prevalence of orthostatic hypotension and autonomic dysreflexia. Although the International Standards for Neurological Classification of SCI evaluate sensorimotor function both above and below the injury level, there are limited quantitative measures for gauging sympathetic outflow and the extent of dysautonomia resulting from neurological damage. Despite studies on the effects of SCI on electrodermal activity (EDA) and blood pressure (BP), there is a lack of detailed feature comparisons involving EDA, skin vasomotor activity, and BP. Therefore, we investigated the relationship between EDA, skin vasomotor, and BP responses to sympathetic activation via median nerve stimulation in persons with and without SCI. Adults with and without SCI (cohort demographics presented in poster) participated in this study. Lead II electrocardiogram (ECG), pneumogram (P), photoplethysmogram (PPG), and EDA were recorded from either the trunk (ECG, P) or both limbs (PPG, EDA). Beat-by-beat BP was recorded from the middle finger of the left hand (VitalStream, CareTaker Medical). Evoked responses in the above signals were measured surrounding a cathodal electrical pulse (30 mA, 200 μs) delivered to the distal right median nerve 1-2 cm proximal and medial to the radial styloid process either during systole or diastole of the cardiac cycle. There were notable differences between baseline signals before and after the experimental session, along with a consistent reduction of limb temperature (> 2° Celsius). Increases in EDA (greater than two standard deviations from baseline) were found across non-SCI participants following stimulation both during systole and diastole, along with skin vasoconstriction following the onset of EDA modulation (> 50% of trials). Individual differences were noted in evoked responses to stimulation at systole vs. diastole. Furthermore, attenuated responses were observed in individuals with SCI. Stimulation caused no evoked signal response habituation across trials within participants. Additionally, evoked BP changes were not consistent across all individuals with respect to stimulation. Our results show a fixed relationship between evoked skin vasomotor and sudomotor responses to single pulse stimuli across participants and had consistent waveform features. Potential individual effects of stimulation delivered at systole vs. diastole warrant an in-depth analysis of reflex gating of sudomotor and skin vasomotor responses. This would present insight into the population with SCI, where dysfunction could greatly exaggerate reflex gating. 1R01NS131493-01. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Periorbital skin pallor due to skin vasoconstriction following 2.5% phenylephrine mydriatic eye drops instillation prior to retinopathy of prematurity treatment in preterm infant.

Periorbital skin pallor due to skin vasoconstriction following 2.5% phenylephrine mydriatic eye drops instillation prior to retinopathy of prematurity treatment in preterm infant.

Abstract 100: Activation Of The Skin Renin-angiotensin System Contributes To The Development Of Hypertension

Recent studies suggest skin vasoconstriction and sodium (Na + ) accumulation are associated with hypertension. The skin has a localized renin-angiotensin system (RAS), a key regulator of blood pressure (BP), but its functional role remains unclear. This study aims to investigate the role of skin RAS in hypertension. Skin tissue from 32 individuals, including patients with hypertension, was used to evaluate the association between skin RAS component expression and office BP. Among the RAS components, skin expression of ATRAP (type-1 angiotensin II (Ang II) receptor (AT1R)-associated protein), which selectively inhibits pathological AT1R signaling, was inversely correlated with systolic and diastolic BP (R 2 = 0.12, P < 0.05; R 2 = 0.20, P < 0.05, respectively). To investigate the causal relationship between skin ATRAP and hypertension, mice lacking ATRAP in skin keratinocytes (KO: K14 Cre ;ATRAP flox ) were generated. Telemetry analysis showed that Ang II (500 ng/kg/min)-induced hypertension and related cardiac hypertrophy was exacerbated in KO mice compared to control mice (mean BP, 123.3 ± 4.7 vs. 132.6 ± 3.1 mmHg, n = 5, P < 0.05; heart/body weight, 4.7 ± 0.4 vs. 5.2 ± 0.7, n = 11-12, P < 0.05). KO mice showed increased skin expression of angiotensinogen and AT1R ( P < 0.05 for each; n = 11-12), while those in the kidneys and heart were similar in both groups, suggesting skin-specific enhancement of tissue RAS activity. AT1R blocker treatment eliminated exaggerated Ang II-induced hypertension and enhancement of skin RAS activity in KO mice. Sympathetic nerve activity, plasma volume, and skin Na + content did not differ between the groups. In KO mice, urine volume per water intake increased ( P < 0.001), despite similar body weight changes in both groups, suggesting decreased extra-renal water loss. Consistent with these findings, skin blood flow (22.6 ± 3.8 vs. 16.5 ± 4.5 AU, P < 0.001) and transepidermal water loss (9.0 ± 1.9 vs. 6.5 ± 1.9 g/m 2 /h, P < 0.01) were decreased in KO mice. These differences, including exaggerated Ang II-induced hypertension, were eliminated by skin vasodilation via body temperature elevation. In conclusion, enhanced skin RAS activity contributes to BP elevation via skin vasoconstriction. Skin RAS may be a novel target for treating hypertension.

손 냉각과 압박이 조합된 항암 치료용 장갑이 손의 혈관 수축 및 국소 감각에 미치는 영향

This study investigated the combined effects of wrist compression and hand cooling on cutaneous vasoconstriction of the hands to develop chemotherapy gloves that alleviate side-effects of anti-cancer treatments. Eight healthy young females (23 ± 3 y in age, 162 ± 4 cm in height, 60 ± 8 kg in weight, 22.6 ± 3.0 kg•mSUP-2/SUP in body mass index, 29.0 ± 6.6 % body fat) participated in the following three experimental conditions: cooling only with 14℃ (CO), cooling & intermittent compression (CIC), and cooling & continuous compression (CCC). The results showed 1) no significant differences in finger skin blood flow(%) or finger skin temperature among the three conditions, 2) no significant difference in hand skin temperature between the CO and CCC or CIC conditions, and 3) no significant differences in overall thermal sensation or thermal comfort among the three conditions. However, subjects felt more wrist and hand pressure and tingle sensations in the CIC (pressure phase) and CCC conditions than in the CO condition (P0.001). In conclusion, we did not find any synergistic effects on hand skin vasoconstriction from adding wrist compression to hand cooling, and the pressure and tingling sensations were deteriorated by adding the compression band. Therefore, we suggest cooling the hands at 14oC during cancer treatments, rather than adding compression with cooling.

Basic physiological effects of ketamine-xylazine mixture as a general anesthetic preparation for rodent surgeries

Among the numerous general anesthetics utilized in rodent surgical procedures, the co-administration of ketamine and xylazine is the current standard for induction and maintenance of surgical planes of anesthesia and pain control. In contrast to classical GABAergic anesthetics, which act to inhibit CNS activity, inducing muscle relaxation, sedation, hypothermia, and brain hypoxia, ketamine and xylazine act through different mechanisms to induce similar effects while also providing potent analgesia. By using three-point thermorecording in freely moving rats, we show that the ketamine-xylazine mixture induces modest brain hyperthermia, resulting from increased intra-cerebral heat production due to metabolic brain activation and increased heat loss due to skin vasodilation. The first effect derives from ketamine, which alone increases brain and body temperatures due to brain metabolic activation and skin vasoconstriction. The second effect derives from xylazine, which increases heat loss due to potent skin vasodilation. By using oxygen sensors coupled with amperometry, we show that the ketamine-xylazine mixture modestly decreases brain oxygen levels that results from relatively weak respiratory depression. This tonic pharmacological effect was preceded by a strong but transient oxygen increase that may result from a stressful injection or unknown, possibly peripheral action of this drug combination. This pattern of physiological effects elicited by the ketamine-xylazine mixture differs from the effects of other general anesthetic drugs, particularly barbiturates.

Emerging topics on basic research in hypertension: interorgan communication and the need for interresearcher collaboration.

The pathogenesis of hypertension is multifactorial and highly complex. Basic research plays critical roles in elucidating the complex pathogenesis of hypertension and developing its treatment. This review covers recent topics in basic research related to hypertension in the following six parts: brain/autonomic nervous system, kidney, vascular system, potential treatments, extracellular vesicles, and gut microbiota. The brain receives afferent nerve inputs from peripheral organs, including the heart, kidneys, and adipose tissue, and humoral inputs from circulating factors such as proinflammatory cytokines and leptin, which are involved in the regulation of central sympathetic outflow. In the kidneys, changes in Wnt/β-catenin signaling have been reported in several hypertensive models. New findings on the renin-angiotensin-aldosterone system in the kidneys have also been reported. Sirtuin 6, which participates in various cellular functions, including DNA repair, has been shown to have protective effects on the vascular system. Skin water conservation, mediated by skin vasoconstriction and the accumulation of osmolytes such as sodium, has been found to contribute to hypertension. Studies of rivaroxaban and sodium-glucose cotransporter-2 inhibitors as drug repositioning candidates have been performed. Extracellular vesicles have been shown to be involved in novel diagnostic approaches and treatments for hypertension as well as other diseases. In gut microbiota studies, interactions between microbiota and antihypertensive drugs and potential pathophysiology linking microbiota and COVID-19 have been reported. It can be seen that inter-organ communication has received particular attention from these recent research topics. To truly understand the pathogenesis of hypertension and to develop treatments for conquering hypertension, interresearcher communication and collaboration should be further facilitated. This mini-review focuses on recent topics on basic research in hypertension from the several points of view. The recent topics indicate that inter-organ communication has received particular attention. Interresearcher communication and collaboration should also be further facilitated to truly understand the complex pathogenesis of hypertension and to develop the treatments.

S-27-2: RENAL WATER LOSS-INDUCED SKIN WATER CONSERVATION LEADS TO HIGH BLOOD PRESSURE IN SPONTANEOUSLY HYPERTENSIVE RATS

Objective: Although previous studies have demonstrated the pathophysiological basis of hypertension in basic and clinical sciences, the decisive mechanism of essential hypertension remains to be clarified. We recently reported that 5/6 nephrectomized rats exhibited renal water loss due to impaired renal concentration ability and that the renal water loss triggered suppression of transepidermal water loss (TEWL). This skin water conservation was achieved by skin vasoconstriction-mediated reduction in skin vascular mass, which increased blood pressure in 5/6 nephrectomized rats. In this study, we examined the effect of renal and skin water handling on high blood pressure in spontaneously hypertensive rats (SHR). Design and method: We used male 9 weeks old SHR and its control normotensive Wistar Kyoto rats (WKY) in this study. The rats were kept in metabolic cages to collect urine for 24 hours. We also collected urine under water deprivation. After the urine collection, the rats were sacrificed and their plasma and tissues were collected. Skin sodium and potassium content were measured by the ashing-flame photometer method. In a separate experiment, we compared blood pressure and TEWL in anesthetized SHR and WKY. Body temperature was raised by elevating room temperature. Results: Compared with WKY, SHR exhibited a significant increase in urine volume and a decrease in urine osmolality. There were no significant differences in plasma osmole concentrations, urinary sodium, potassium, and urea excretion between the groups. SHR showed significantly higher urine volume and lower urine osmolarity than WKY even in water deprivation, suggesting that SHR has renal water loss. SHR exhibited significantly lower TEWL and higher blood pressure and skin sodium and potassium content compared with WKY. Skin vasodilation induced by elevating body temperature significantly reduced blood pressure in SHR but not WKY. Conclusions: These findings suggest that renal water loss due to the impaired renal concentration ability induces suppression of TEWL and skin osmole accumulation in SHR. This skin water conservation leads to high blood pressure via skin vasoconstriction to reduce skin vascular mass and TEWL. Skin water conservation as a compensatory mechanism for renal water loss may be a key mechanism and novel therapeutic target for essential hypertension.

Contributions of renal water loss and skin water conservation to blood pressure elevation in spontaneously hypertensive rats.

We recently reported that skin vasoconstriction to suppress transepidermal water loss (TEWL) leads to hypertension in renal injury model rats with impaired urine concentration ability. In this study, we investigated the pathogenesis of hypertension in spontaneously hypertensive rats (SHRs) from the perspective of renal water loss and skin water conservation. We compared the urinary concentration ability, body sodium and water balance, blood pressure, and TEWL in SHRs and control normotensive Wistar-Kyoto rats (WKYs). SHRs showed significantly higher urine volume and lower urinary osmolality than those of WKYs, while there were no significant differences in water intake, urinary osmolyte excretion, and plasma osmolarity between the groups. SHRs exhibited significantly higher blood pressure, skin sodium content, and lower TEWL compared with those is WKYs. Skin vasodilation, induced by elevating body temperature, increased TEWL in both SHRs and WKYs, and significantly reduced blood pressure in SHRs but not WKYs. These findings suggest that physiological adaptation can reduce dermal water loss in SHRs to compensate for renal water loss. Vasoconstriction required for successful cutaneous water conservation explains SHR hypertension. Renal concentration ability and skin barrier function for water conservation may become a novel therapeutic target for essential hypertension.

β2-adrenoreceptors control human skin microvascular reactivity.

Topical α1- and α2-adrenoreceptor (ADRA1 and 2) agonists are effective in alleviating permanent vasodilation and facial erythema associated with rosacea by inducing skin vasoconstriction. Although β-adrenoreceptor (ADRB) antagonists are used off-label for rosacea, pharmacological and pharmacodynamic data pertaining to these receptors in skin micro-vessels are lacking. Objectives: To analyse the expression of different adrenergic receptors and their contribution to vasoreactivity in skin micro-vessels. Small arteries (500-800μm) and arterioles (<200μm) were studied in human foreskin tissue. Specifically, ADR-A1, -A2, -B1 and -B2 expression was assayed by immunofluorescence, polymerase chain reaction (PCR), and western blotting. Small skin artery reactivity was evaluated using ex vivo myography (500-800μm) or a visible microscope perfusion system with precision-cut skin slices (<200μm). ADRB2 was the most highly expressed receptor in small skin arteries and arterioles, followed by ADRA2. ADRA2 activation via brimonidine-induced vasoconstriction was greater in skin arterioles than in small skin arteries, and more potent than that with norepinephrine (NE). The use of prazosin (ADRA1 inhibitor) partially attenuated brimonidine-induced vasoconstriction, indicating some activation of ADRA1 by brimonidine, at least at 10-μM concentrations. Small skin arteries and arterioles, pre-treated with prazosin and stimulated with NE, exhibited ADRB2-mediated vasodilation, which was inhibited by the beta blockers, propranolol or timolol. This study shows that ADRB2 is predominantly expressed in small skin arteries and arterioles, and that ADRBs plays a functional role in vasodilation. The data presented here indicate that ADRBs can be a therapeutic target for the treatment of rosacea.

A simplified approach to describe the mean skin temperature variations during prolonged running exercise.

Skin blood flow and skin temperature play a fundamental role in the thermoregulatory processes and are expected to largely change in response to a prolonged running exercise. The skin temperature changes have been documented in the literature, mainly through infrared thermographic measurements performed before, after, and, in a limited number of studies, during the exercise. After an initial reduction probably ascribed to skin vasoconstriction, the further skin temperature modifications with time, measured in reference papers during a steady and prolonged run, do not show a common behaviour, probably due to different exercise intensities and environmental conditions reported in these studies. This research aimed to develop a simplified method for describing the skin temperature changes during running exercise through the theoretical solutions of the dynamic energy balance of the human body in the early and late time periods, i.e., close to the onset and the end of exercise. These two asymptotic solutions for the skin temperature, having a largely dissimilar trend, collide at a time instant likely associated with the switch from skin vasoconstriction to vasodilation. Examples of application of the proposed method, based on the intersection of asymptotes, were provided. It was also demonstrated its capability to interpret the experimental skin temperature variations with time for constant-load running exercises reported in the literature under different levels of exercise intensity and environmental conditions.

Involvement of brainstem noradrenergic system in cutaneous heat loss during exercise

The involvement of brainstem noradrenergic system in thermoregulation during exercise was evaluated by assessing the neuronal activation of A1, A2, locus coeruleus (LC) during exercise. Male Wistar rats weighing 280−330 g were used in the present study. Ninety minutes after exercise bout until fatigue, animals were anaesthesiated and brain removed and processed immunohistochemically for Fos protein and tyrosine hydroxylase in A1, A2 and LC and for Fos in POA subregions. Core and tail temperature were recorded during all running period by telemetry system. Heat storage rate (HSR, cal.min−1), maximum tail vasoconstriction (°C) and vasodilatation threshold (°C) were calculated and correlated with Fos expression in all nuclei studied. Fos expression in LC correlated inversely with maximum tail skin vasoconstriction (r = −0.787, p < 0.03) and HSR (r = −0.834, p < 0.02) and positively to time to fatigue (r = 0.862, p < 0.01). A1 nucleus showed an inverse correlation with tail skin vasodilatation threshold (r = −0.861, p < 0.01). Fos expression in LC correlated inversely with Fos expression in the median (MnPO, r = −0.909, p < 0.01) and medial preoptic nucleus (MPOM, r = −0.942, p < 0.05). Our results bring further evidences that noradrenergic neurons from LC and A1 nuclei are involved in cutaneous heat loss mechanisms during exercise. LC nucleus probably modulates the sympathetic tonus of tail artery and integrates the central network LC / POA that could represent an important circuitry of temperature regulation during exercise. Also, noradrenergic neurons from A1 nucleus could be involved in cutaneous heat loss during exercise by modulating of vasodilatation threshold.

Inhibition of PDE4 Induces Hypothermia in Mice

Type 4 cyclic nucleotide phosphodiesterases (PDE4s), a group of isoenzymes that hydrolyze and inactivate the second messenger cAMP, are established targets for development of enzyme inhibitors with anti‐inflammatory properties. While testing the anti‐inflammatory effects of a nonselective PDE4 inhibitor in a murine model of bacterial lung infection, we noticed that PDE4 inhibition per se induced significant hypothermia in the animals in the absence of bacterial infection. Because drug‐induced hypothermia may critically impact our animal model, and the role cAMP‐phosphodiesterases play in the regulation of body temperature is poorly understood, we further explored this observation. We found that treatment with a number of structurally distinct PAN‐PDE4 inhibitors, including Rolipram, Roflumilast and RS25344 (all 1 mg/kg, i.p.), but not the PDE3‐selective inhibitor Cilostamide, induced a rapid decrease in core body temperature of C57Bl6 mice as measured with a rectal thermometer at 30 min after drug application, suggesting that hypothermia in mice is a class‐effect of PDE4 inhibitors. PDE4 inhibitor‐induced hypothermia was considerable (~4°C drop), rapid in onset (max effect is reached within 20–30 min), and long lasting (core body temperature remains below controls for up to 5 h). As little as 40 μg/kg of the archetypal PDE4 inhibitor Rolipram induced a hypothermic effect. Similar or higher doses of Rolipram were used in most published animal studies. Thus, the reported findings are likely associated with, or at least paralleled by, drug‐induced hypothermia. The initial decrease in body temperature after PDE4 inhibitor injection is so rapid that it is no different from heat dissipation after euthanasia, suggesting that PDE4 inhibition affects central body temperature regulation so that both heat‐generating (e.g. shivering/non‐shivering thermogenesis) as well as heat‐preserving (e.g. skin vasoconstriction) mechanisms are simultaneously suspended, either by lowering the cold defense set point or by impairing its enforcement. Indeed, PDE4 inhibitor treatment induced a temporary heat‐loss via tail vasodilation as assessed by thermography. Consistent with the idea of an effect on central body temperature regulation, hypothermia was induced by moderate doses (≤1 mg/kg) of various brain‐penetrant PDE4 inhibitors. Conversely, YM976, a PDE4 inhibitor that does not cross the blood‐brain barrier, had no effect. Finally, to begin delineating the mechanism of drug‐induced hypothermia, we show that a blockade of serotonergic‐ and dopaminergic‐, but not β‐adrenergic‐, histaminergic‐ or opiate receptors, can alleviate PDE4 inhibitor‐induced hypothermia.Support or Funding InformationSupported by grants from the Cystic Fibrosis Foundation (SALEH18H0,RICHTE16GO) and the NIH (HL76125, HL141473, HL066299).

No Evidence of Heat-Induced Vasoconstriction in Human Skin Using Ultrasound Doppler after Passive Whole-Body Heat Stress

No Evidence of Heat-Induced Vasoconstriction in Human Skin Using Ultrasound Doppler after Passive Whole-Body Heat Stress

Perioperative temperature management in adult anesthesia

Body temperature management is very important to be controlled in surgery because there are so many effects that can be caused due to uncontrolled body temperature during operations such as decreased heart rate, breathing frequency and blood pressure, the skin becomes cyanotic, and even can cause disturbance of consciousness. The body already has a mechanism that can reduce the risk of a decrease in temperature during surgery such as skin vasoconstriction, changes in behavior, shivering and non-shivering thermogenesis. Many factors can influence changes in body temperature thermoregulation in the operating room such as operating room temperature, area of surgery wound, fluid, age, anesthesia, and the duration of the operation, so that we need to know perioperative temperature management.

Chapter 11 - Skin vasoconstriction as a heat conservation thermoeffector

Cold exposure stimulates heat production and conservation to protect internal temperature. Heat conservation is brought about via reductions in skin blood flow. The focus, here, is an exploration of the mechanisms, particularly in humans, leading to that cutaneous vasoconstriction. Local skin cooling has several effects: (1) reduction of tonic nitric oxide formation by inhibiting nitric oxide synthase and element(s) downstream of the enzyme, which removes tonic vasodilator effects, yielding a relative vasoconstriction; (2) translocation of intracellular alpha-2c adrenoceptors to the vascular smooth-muscle cell membrane, enhancing adrenergic vasoconstriction; (3) increased norepinephrine release from vasoconstrictor nerves; and (4) cold-induced vasodilation, seen more clearly in anastomoses-rich glabrous skin. Cold-induced vasodilation occurs in nonglabrous skin when nitric oxide synthase or sympathetic function is blocked. Reflex responses to general body cooling complement these local effects. Sympathetic excitation leads to the increased release of norepinephrine and its cotransmitter neuropeptide Y, each of which contributes significantly to the vasoconstriction. The contributions of these two transmitters vary with aging, disease and, in women, reproductive hormone status. Interaction between local and reflex mechanisms is in part through effects on baseline and in part through removal of the inhibitory effects of nitric oxide on adrenergic vasoconstriction.

Inflow of oxygen and glucose in brain tissue induced by intravenous norepinephrine: relationships with central metabolic and peripheral vascular responses.

As an essential part of sympathetic activation that prepares the organism for "fight or flight," peripheral norepinephrine (NE) plays an important role in regulating cardiac activity and the tone of blood vessels, increasing blood flow to the heart and the brain and decreasing blood flow to the organs not as necessary for immediate survival. To assess whether this effect is applicable to the brain, we used high-speed amperometry to measure the changes in nucleus accumbens (NAc) levels of oxygen and glucose induced by intravenous injections of NE in awake freely moving rats. We found that NE at low doses (2-18 μg/kg) induces correlative increases in NAc oxygen and glucose, suggesting local vasodilation and enhanced entry of these substances in brain tissue from the arterial blood. By using temperature recordings from the NAc, temporal muscle, and skin, we show that this central effect is associated with strong skin vasoconstriction and phasic increases in intrabrain heat production, indicative of metabolic neural activation. A tight direct correlation between NE-induced changes in metabolic activity and NAc levels of oxygen and glucose levels suggests that local cerebral vasodilation is triggered via a neurovascular coupling mechanism. Our data suggest that NE, by changing vascular tone and cardiac activity, triggers a visceral sensory signal that rapidly reaches the central nervous system via sensory nerves and induces neural activation. This neural activation leads to a chain of neurovascular events that promote entry of oxygen and glucose in brain tissue, thus preventing any possible metabolic deficit during functional activation. NEW & NOTEWORTHY Using high-speed amperometry and thermorecording in freely moving rats, we demonstrate that intravenous norepinephrine at physiological doses induces rapid correlative increases in nucleus accumbens oxygen and glucose levels coupled with increased intrabrain heat production. Although norepinephrine cannot cross the blood-brain barrier, by changing cardiac activity and vascular tone, it creates a sensory signal that reaches the central nervous system via sensory nerves, induces neural activation, and triggers a chain of neurovascular events that promotes intrabrain entry of oxygen and glucose.

Brain temperature effects of intravenous heroin: State dependency, environmental modulation, and the effects of dose

Here we examined how intravenous heroin at a dose that maintains self-administration (0.1 mg/kg) affects brain temperature homeostasis in freely moving rats under conditions that seek to mimic some aspects of human drug use. When administered under standard laboratory conditions (quiet rest at 22 °C ambient temperature), heroin induced moderate temperature increases (1.0–1.5 °C) in the nucleus accumbens (NAc), a critical structure of the brain motivation-reinforcement circuit. By simultaneously recording temperatures in the temporal muscle and skin, we demonstrate that the hyperthermic effects of heroin results primarily from inhibition of heat loss due to strong and prolonged skin vasoconstriction. Heroin-induced brain temperature increases were enhanced during behavioral activation (i.e., social interaction) and in a moderately warm environment (29 °C). By calculating the “net” effects of the drug in these two conditions, we found that this enhancement results from the summation of the hyperthermic effects of heroin with similar effects induced by either social interaction or a warmer environment. When the dose of heroin was increased (to 0.2, 0.4, 0.8, 1.6, 3.2, and 6.4 mg/kg), brain temperature showed a biphasic down-up response. The initial temperature decrease was dose-dependent and resulted from a transient inhibition of intra-brain heat production coupled with increased heat loss via skin surfaces—the effects typically induced by general anesthetics. These initial inhibitory effects induced by large-dose heroin injections could be related to profound CNS depression—the most serious health complications typical of heroin overdose in humans.

2-Ethylpyrazine Induces Vasodilatation by Releasing Nitric Oxide in the Endothelium.

Oxygen transportation and regulation of some physiological processes are facilitated by blood flow. Furthermore, blood flow is regulated by various factors such as nitric oxide (NO) and the autonomic nerve system. In modern life, many people suffer from chilliness (hiesho) because of mental stress and an excessive use air-conditioning systems, which induces vasoconstriction in the peripheral skin. In this study, we focused on pyrazine derivatives, particularly compounds that are used as food flavoring materials, and investigated their effects on vascular function and blood flow. We examined the vasodilatory effect of pyrazine derivatives in the rat thoracic aorta and found 2-ethylpyrazine (2-EP) to be the most active pyrazine compound. Additionally, we found that 2-EP induces vasodilatation through the activities of endothelium-derived relaxing factors. 2-EP activates NO synthesis through the effect of endothelial NO synthase in the endothelium. As a result, cyclic GMP levels rise in smooth muscle cells and vasodilatation is induced. We also confirmed that 2-EP increases peripheral blood flow in rats. From these results, we concluded that 2-EP induces vasodilatation by inducing the release of NO and increasing peripheral blood flow.

Characterizing human skin blood flow regulation in response to different local skin temperature perturbations

Small nerve fibers regulate local skin blood flow in response to local thermal perturbations. Small nerve fiber function is difficult to assess with classical neurophysiological tests. In this study, a vasomotor response model in combination with a heating protocol was developed to quantitatively characterize the control mechanism of small nerve fibers in regulating skin blood flow in response to local thermal perturbation.The skin of healthy subjects' hand dorsum (n=8) was heated to 42°C with an infrared lamp, and then naturally cooled down. The distance between the lamp and the hand was set to three different levels in order to change the irradiation intensity on the skin and implement three different skin temperature rise rates (0.03°C/s, 0.02°C/s and 0.01°C/s). A laser Doppler imager (LDI) and a thermographic video camera recorded the temporal profile of the skin blood flow and the skin temperature, respectively.The relationship between the skin blood flow and the skin temperature was characterized by a vasomotor response model. The model fitted the skin blood flow response well with a variance accounted for (VAF) between 78% and 99%. The model parameters suggested a similar mechanism for the skin blood flow regulation with the thermal perturbations at 0.03°C/s and 0.02°C/s. But there was an accelerated skin vasoconstriction after a slow heating (0.01°C/s) (p-value<0.05). An attenuation of the skin vasodilation was also observed in four out of the seven subjects during the slow heating (0.01°C/s). Our method provides a promising way to quantitatively assess the function of small nerve fibers non-invasively and non-contact.