Increased Plasma Epinephrine Research Articles

Elevated sympathoadrenal response following active ascent to 3,600m is not associated with acute mountain sickness

Previous reports have suggested an increase in plasma epinephrine (EPI) and either an increase, no change or decrease in norepinephrine (NE) following acute (< 4 h) exposure to high altitude (HA). In addition, previous research has demonstrated an exercise-induced increase in EPI and NE during exercise initiated following arrival at HA. Last, some but not others have reported an association between increased sympathoadrenal activity and acute mountain sickness (AMS). We hypothesized that elevated sympathoadrenal activity induced from active ascent on foot to 3,600m may contribute to the development of AMS. Thirty-seven Soldiers (mean ± SD; 6 women; age=25.5±4.9 years) were tested at their baseline residence (BLR; Fort Bliss, TX, 1,190m), transported to Taos, NM (2,845m), then hiked (n=18) or were driven (n=19) to the HA data collection site where they resided for four days (68hrs). AMS Cerebral Factor Score (AMS-C) was determined using the Environmental Symptoms Questionnaire (ESQ-III) recorded twice at HA on day 1 (HA1), five times on days 2 (HA2) and 3 (HA3) and once on day 4 (HA4). If AMS-C was ≥0.7 on any measurement occasion, individuals were categorized as AMS-susceptible (AMS+, n=11) others were AMS-resistant (AMS─, n=26). Plasma EPI (pg/ml) and NE (pg/ml) were measured from venous blood draws at 06:00 at BLR, a non-fasted blood draw at 18:00 following ascent on HA1, and subsequent fasted blood samples at 06:00 on each morning at HA (HA2, HA3, HA4). AMS-susceptibility was not associated with the EPI or NE response in any condition so both cohorts were combined. The EPI response to active vs. passive ascent was similar with an increase (p<0.05) from BLR (28.0±26.8) to HA1 (47.5±40.3) followed by a subsequent decrease (p<0.05) from HA1 to HA2 (28.0±18.6) through HA4 (25.4±16.9). NE, however, increased (p<0.05) only in the active ascent group from BLR (413±216) to HA1 (729±281) and remained stable from HA1 through HA4 (644±192). The passive ascent group demonstrated no change in NE from BLR (327±126) to HA1 (413±181) through HA4 (466±144). NE levels were similar (p>0.05) in the active vs passive ascent group at BLR but higher (p<0.05) in the active ascenders on HA1 through HA4. In conclusion, contrary to our hypothesis, the sympathoadrenal response to HA was not impacted by AMS susceptibility but active ascent induced a greater NE response following ascent and throughout the duration of the HA stay. USAMRDC. Authors’ views not offcial U.S. Army or DoD policy. 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.

Effects of Renal Denervation on Ouabain‐Induced Hypertension in Rats

Background. Ouabain, a Na+, K+‐ATPase inhibitor, is elevated in hypertensive patients. Evidence suggests ouabain contributes to hypertension mainly through activation of the sympathetic nervous system (SNS). Renal nerves play a vital role in the regulation of SNS activity, so we hypothesize that renal denervation may attenuate the development of ouabain‐induced hypertension. Methods and Results. Forty Sprague‐Dawley rats were divided into following groups (n = 10 each): control group (sham surgery plus intraperitoneal saline injection), RDN group (renal denervation (RDN) plus intraperitoneal saline injection), ouabain group (sham surgery plus intraperitoneal ouabain injection), and ouabain + RDN group (RDN plus intraperitoneal ouabain injection). After eight weeks, compared with the control group, rats in the ouabain group exhibited elevated blood pressure (P < 0.05), increased plasma epinephrine, norepinephrine, angiotensin II, and aldosterone levels (P < 0.05). These indexes could be significantly ameliorated by RDN. RDN also reduced the thickening of aortic tunica media and downregulated the expression of proliferating cell nuclear antigen (PCNA) in the thoracic aorta induced by ouabain. Masson staining and echocardiography showed that myocardial fibrosis and increased left ventricular mass in the ouabain group could be attenuated by RDN. Conclusions. The present study reveals that renal nerves play an important role in the development of ouabain‐induced hypertension. RDN could inhibit the pressor effect and the myocardial remodeling induced by ouabain potentially via inhibiting catecholamine release and vascular smooth muscle cell proliferation. Clinical studies are needed to explore whether RDN may exhibit better antihypertensive effects on hypertensive patients with high plasma ouabain levels as compared to those with normal plasma ouabain levels.

Fasting for 48h induced similar glucose intolerance in both sexes despite greater perceived stress and decreased estradiol levels in females.

The purpose of this study was to compare the effects of fasting for 48 h on the evoked insulin and glucose responses in males and females, and to explore factors such as stress and estrogen levels that might influence these responses. Healthy, nonobese male (n = 14) and female (n = 14) subjects underwent 48-h fasting trial. Changes in glucose tolerance and insulin levels in response to the oral glucose tolerance test, subjectively perceived stress and catecholamine concentrations were measured in all participants. Estrogen levels were also measured in the female participants during the 48-h fast. Glucose area under the curve (AUC) values increased similarly in both sexes after 48-h fasting (P < 0.05), but females displayed a greater rise in insulin AUC values than males (P < 0.05). Fasting increased plasma epinephrine concentrations in both sexes (P < 0.05), whereas plasma norepinephrine concentrations and subjective stress increased only in females (P < 0.05). Plasma 17-β-estradiol concentrations in females decreased after fasting (P < 0.05). Fasting for 48h induced a similar glucose intolerance in females and males, despite decreased 17-β-estradiol levels and greater psychological and physiological stress in females. These differences represent a plausible explanation for the gender-based differences observed in insulin responses. Retrospectively registered on ClinicalTrials.gov(NCT05545943) in September 19, 2022.

Yokukansan, a Traditional Japanese Medicine, Suppresses Stress-Induced Sympathetic Activation via Central Responses in Rats

Objectives: Yokukansan (YKS) is a traditional Japanese Kampo medicine approved by the Ministry of Health, Labour and Welfare of Japan. Recently, in addition to its indications as a drug treatment, YKS has been shown to have ameliorative effects on various psychological and behavioral responses such as anxiety, aggression, and stress responses. Stress exposure activates not only the hypothalamic–pituitary–adrenal axis but also the sympathetic nervous system. Sympathetic activation in brain regions such as the paraventricular hypothalamic nucleus (PVN) stimulates elevation of plasma catecholamine (noradrenaline and adrenaline) levels. We previously reported that various stress-related neuropeptides and several kinds of stressors, such as restraint stress (RS), increase plasma catecholamine and that brain prostanoids and their synthases mediate these responses in rats. In the present study, to determine if YKS treatment can affect stress-induced sympathetic activation, we examined the effects of YKS treatment on the RS-induced elevation of plasma catecholamine levels and related prostanoid production in the PVN of rats. Methods: YKS (1000 mg/10 mL/kg, p.o.) or vehicle was administered to rats daily for 14 days, and all rats were exposed to RS for 60 min on day 14. Before and during stress exposure on day 14, blood samples and PVN dialysates were collected and analyzed by high-performance liquid chromatography and liquid chromatography-ion trap tandem mass spectrometry, respectively. Results: Our results showed that repeated administration of YKS suppressed the RS-induced increase in plasma adrenaline but not noradrenaline. Furthermore, YKS administration also suppressed the RS-induced elevation of both prostaglandin E2 and thromboxane B2 levels in the PVN. In addition, we found that repeated administration of YKS suppressed the RS-induced increase in serotonin, gamma-aminobutyric acid, and acetylcholine in the PVN. Conclusion: Our results suggest that YKS can ameliorate stress-induced sympathetic activation via inhibition of stress responses in the brain.

Insulin enhances contextual fear memory independently of its effect in increasing plasma adrenaline

AimsAdrenaline enhances contextual fear memory consolidation possibly by activating liver β2-adrenoceptors causing transient hyperglycaemia. Contrastingly, insulin-induced hypoglycaemia may culminate in blood adrenaline increment, hidering the separation of each hormone's action in contextual fear memory. Therefore, an adrenaline-deficient mouse model was used aiming to investigate if contextual fear memory consolidation following insulin administration requires or not subsequent increases in plasma adrenaline, which occurs in response to insulin-induced hypoglycemia. Main methodsFear conditioning was performed in wild-type (WT) and adrenaline-deficient (Pnmt-KO) male mice (129 × 1/SvJ) treated with insulin (2 U/kg, intraperitoneal (i.p.)) or vehicle (0.9 % NaCl (i.p.)). Blood glucose was quantified. Catecholamines were quantified using HPLC with electrochemical detection. Quantitative real-time polymerase chain reaction was used to assess mRNA expression of hippocampal Nr4a1, Nr4a2, Nr4a3, and Bdnf genes. Key findingsInsulin-treated WT mice showed increased freezing behaviour when compared to vehicle-treated WT mice. Also, plasma dopamine, noradrenaline, and adrenaline increased in this group. Insulin-treated Pnmt-KO animals showed increased freezing behaviour when compared with respective vehicle. However, no changes in plasma or tissue catecholamines were identified in insulin-treated Pnmt-KO mice when compared with respective vehicle. Furthermore, insulin-treated Pnmt-KO mice presented increased Bdnf mRNA expression when compared to vehicle-treated Pnmt-KO mice. SignificanceConcluding, enhanced freezing behaviour after insulin treatment, even in adrenaline absence, may indicate a key role of insulin in contextual fear memory. Insulin may cause central molecular changes promoting contextual fear memory formation and/or retrieval. This work may indicate a further role of insulin in the process of contextual fear memory modulation.

Renal and Endocrine Responses to Arm Exercise in Persons with Cervical Spinal Cord Injury

The aim of this study was to assess renal functions and endocrine responses to arm exercise in persons with cervical spinal cord injury (CSCI) under euhydrated conditions (free drinking of water), and to determine the physiological effects of exercise on renal function in these subjects. Eleven CSCI individuals (spinal lesions between C6 and C8, American Spinal Injury Association impairment scale A) and nine able-bodied (AB) persons rested for 30 min before performing 30 min arm-crank ergometer exercises at 50% of their maximum oxygen consumption, followed by 60-min of rest/recovery. Urine and blood samples were collected before and immediately after the exercise and recovery period. The CSCI patients showed no increase in plasma adrenaline and plasma renin activity compared with the AB controls, but showed similar changes in plasma aldosterone and the plasma antidiuretic hormone in response to the exercise. Creatinine clearance, osmolal clearance, free water clearance, and the fractional excretion of Na+ did not change during exercise in both groups of subjects, however free water clearance in the CSCI group was higher than in the AB group throughout the study. These findings suggested that activated plasma aldosterone without an increase in adrenaline or renin activity during exercise in CSCI individuals may reflect an adaptation to the disturbance of the sympathetic nervous system to compensate for renal function. As a result, no adverse effects of exercise on renal function in CSCI patients were observed.

E-cigarette aerosol impairs male mouse skeletal muscle force development and prevents recovery from injury.

To date, there has been a lag between the rise in E-cigarette use and an understanding of the long-term health effects. Inhalation of E-cigarette aerosol delivers high doses of nicotine, raises systemic cytokine levels, and compromises cardiopulmonary function. The consequences for muscle function have not been thoroughly investigated. The present study tests the hypothesis that exposure to nicotine-containing aerosol impairs locomotor muscle function, limits exercise tolerance, and interferes with muscle repair in male mice. Nicotine-containing aerosol reduced the maximal force produced by the extensor digitorum longus (EDL) by 30%-40% and, the speed achieved in treadmill running by 8%. Nicotine aerosol exposure also decreased adrenal and increased plasma epinephrine and norepinephrine levels, and these changes in catecholamines manifested as increased muscle and liver glycogen stores. In nicotine aerosol exposed mice, muscle regenerating from overuse injury only recovered force to 80% of noninjured levels. However, the structure of neuromuscular junctions (NMJs) was not affected by e-cigarette aerosols. Interestingly, the vehicle used to dissolve nicotine in these vaping devices, polyethylene glycol (PG) and vegetable glycerin (VG), decreased running speed by 11% and prevented full recovery from a lengthening contraction protocol (LCP) injury. In both types of aerosol exposures, cardiac left ventricular systolic function was preserved, but left ventricular myocardial relaxation was altered. These data suggest that E-cigarette use may have a negative impact on muscle force and regeneration due to compromised glucose metabolism and contractile function in male mice.NEW & NOTEWORTHY In male mice, nicotine-containing E-cigarette aerosol compromises muscle contractile function, regeneration from injury, and whole body running speeds. The vehicle used to deliver nicotine, propylene glycol, and vegetable glycerin, also reduces running speed and impairs the restoration of muscle function in injured muscle. However, the predominant effects of nicotine in this inhaled aerosol are evident in altered catecholamine levels, increased glycogen content, decreased running capacity, and impaired recovery of force following an overuse injury.

Activation of Sympathetic Nervous System Contributes to Erthroprotein Gene Upregulation by Hypobaric Hypoxia

Hypobaric hypoxia (HH) experienced at high altitude initiates a series of physiological adaptations to maintain homeostasis. One such adaptation is the activation of the Epo gene which encodes the glycoprotein hormone erythropoietin (EPO). Increased circulating EPO levels defend against HH by facilitating blood O2 transport through increasing red blood cell production. HH also increases blood pressure (BP) through activation of the sympathetic nervous system and the ensuing elevation of circulating catecholamine levels. The present study examined the role of sympathetic nerve activation in HH‐evoked Epo gene activation and elevated circulating levels of EPO. Studies were performed on adult, male wild‐type (WT) mice treated with 18 hours of HH (0.4 atmospheres), simulating low O2 condition experienced at high altitude. Our results showed increased renal Epo gene abundance and elevated plasma EPO levels. Remarkably, these responses were either markedly attenuated or absent in mice with selective ablation of adrenal medulla as well as after treatment with propranolol, a non‐selective beta‐adrenergic receptor blocker. Moreover, infusion of epinephrine alone activated renal Epo gene and elevated plasma EPO levels. These results suggest that sympathetic nerve activation and the ensuing increase in plasma epinephrine contribute to Epo gene activation by HH.

Nobiletin enhances plasma Interleukin-6 and C-X-C motif chemokine ligand 1 levels that are increased by treadmill running.

Exercise increases the muscular secretion of Interleukin‐6 (IL‐6), which is partially regulated by β2‐adrenergic receptor signaling. Nobiletin is a polymethoxyflavone (PMF) found in citrus fruits that induces the secretion of IL‐6 from C2C12 myotubes, but it remains unclear whether nobiletin promotes IL‐6 secretion during exercise. The aim of this study was to clarify the effects of nobiletin on IL‐6 secretion during exercise. Nobiletin and epinephrine were found to synergistically increase IL‐6 secretion from differentiated C2C12 cells, which was suppressed by the inhibition of adenylyl cyclase (AC) or protein kinase A (PKA). Treadmill running for 60 min increased plasma levels of IL‐6, epinephrine, and norepinephrine in rats. Nobiletin (5 mg/kg) orally administered 30 min before running increased plasma IL‐6 levels further, although it did not increase plasma epinephrine and norepinephrine. In a similar manner to IL‐6, nobiletin and epinephrine synergistically increased the secretion of C‐X‐C motif chemokine ligand 1 (CXCL‐1) from C2C12 cells, or the increase in plasma CXCL‐1 was enhanced by nobiletin after treadmill running of rats. Our results suggest that nobiletin promotes IL‐6 and CXCL‐1 secretion from skeletal muscle by synergistic enhancement of the PKA pathway in β2‐adrenergic receptor signaling.

The Effects of Cold Exposure Training and a Breathing Exercise on the Inflammatory Response in Humans: A Pilot Study.

ABSTRACTObjectiveWe previously showed that a training intervention comprising a combination of meditation, exposure to cold, and breathing exercises enables voluntary activation of the sympathetic nervous system, reflected by profoundly increased plasma epinephrine levels, and subsequent attenuation of the lipopolysaccharide (LPS)-induced inflammatory response. Several elements of the intervention may contribute to these effects, namely, two different breathing exercises (either with or without prolonged breath retention) and exposure to cold. We determined the contribution of these different elements to the observed effects.MethodsForty healthy male volunteers were randomized to either a short or an extensive training in both breathing exercises by either the creator of the training intervention or an independent trainer. The primary outcome was plasma epinephrine levels. In a subsequent study, 48 healthy male volunteers were randomized to cold exposure training, training in the established optimal breathing exercise, a combination of both, or no training. These 48 participants were subsequently intravenously challenged with 2 ng/kg LPS. The primary outcome was plasma cytokine levels.ResultsBoth breathing exercises were associated with an increase in plasma epinephrine levels, which did not vary as a function of length of training or the trainer (F(4,152) = 0.53, p = .71, and F(4,152) = 0.92, p = .46, respectively). In the second study, the breathing exercise also resulted in increased plasma epinephrine levels. Cold exposure training alone did not relevantly modulate the LPS-induced inflammatory response (F(8,37) = 0.60, p = .77), whereas the breathing exercise led to significantly enhanced anti-inflammatory and attenuated proinflammatory cytokine levels (F(8,37) = 3.80, p = .002). Cold exposure training significantly enhanced the immunomodulatory effects of the breathing exercise (F(8,37) = 2.57, p = .02).ConclusionsThe combination of cold exposure training and a breathing exercise most potently attenuates the in vivo inflammatory response in healthy young males. Our study demonstrates that the immunomodulatory effects of the intervention can be reproduced in a standardized manner, thereby paving the way for clinical trials.Trial Registration:ClinicalTrials.gov identifiers: NCT02417155 and NCT03240497.

Cardiac AT 1 Receptor/β‐Arrestin Pathway is a Neonatal‐Specific Druggable Target for Pediatric Heart Failureβ

We recently found a novel neonatal-specific inotropic signaling pathway in murine cardiac myocytes (CMs): strong, long-lasting activation of L-type Ca2+ channels (LTCC) through AT1 receptor (AT1R), β-arrestin 2, and casein kinase 2α’. A peptidyl β-arrestin-biased AT1R agonist (BBA) activates β-arrestin and inhibits G protein after binding to AT1R. Taking our recent above finding into account, its effect was re-analyzed in neonatal mice and human induced pluripotent cell-derived CMs (hiPSC-CMs). BBA caused a significant long-acting positive inotropic but not chronotropic effect in neonatal mice. BBA significantly increased plasma adrenaline (but not serum aldosterone) levels. However, its inotropic effect was mediated by the cardiac AT1R/β-arrestin/LTCC pathway but not adrenaline. BBA significantly increased the peak twitch Ca2+ transients in isolated mouse neonatal ventricular CMs (mNVCMs) as well as hiPSC-CMs exhibiting fetal to neonatal phenotype. It moderately increased unloaded oxygen consumption of spontaneously beating mNVCMs by ~30% but not oxidative stress in the neonatal heart. BBA also significantly enhanced the contractility of the compromised heart of neonatal knock-in mice bearing a point mutation causing human congenital DCM. Therefore, cardiac AT1 receptor /β-arrestin pathway is a neonatal-specific druggable target for pediatric heart failure.

The Effects of Acute Glucoprivation on Adrenomedullary Function in SHR and WKY Rats

We have shown previously, acute intraperitoneal administration of 2-deoxy-d-glucose (2DG) into Sprague-Dawley rats led to activation of the adrenal medulla chromaffin cells, indicated with increased protein kinase activity and increased tyrosine hydroxylase (TH) phosphorylation, as well as increased plasma adrenaline and glucose levels. Here we have used spontaneous hypertensive (SHR) and Wistar Kyoto (WKY) rats to investigate whether hypertension alters basal adrenal chromaffin cell function, or the response of these cells to acute 2DG treatment. At basal level, we found no differences in adrenal medulla TH protein, TH phosphorylation, TH activity or catecholamine levels between SHR and WKY despite a significant difference in the level of systolic blood pressure; nor were there differences in plasma catecholamine levels or blood glucose (BG). Furthermore, the vehicle animals evoked no significant changes in any parameter measured in SHR, but evoked significant increases in pSer19TH, plasma adrenaline and BG in WKY. Single episode of glucoprivation evoked increases in PKA and CDK/MAPK, pSer40TH, pSer31TH, TH activity, and plasma adrenaline and BG in SHR, and in addition evoked increases in PKC, CAMKII, and pSer19TH in WKY. These findings are significant which indicates hypertension does not impact catecholamine function in the adrenal gland. It also appears that hypertension does not alter the adrenal response to glucoprivation. The findings are also significant as WKY showed greater adrenal activation of protein kinases and TH phosphorylation in response to saline and 2DG when compared to SHR and possible reasons for these findings are further discussed.

A Comparison of Hematological, Immunological, and Stress Responses to Capture and Transport in Wild White Rhinoceros Bulls (Ceratotherium simum simum) Supplemented With Azaperone or Midazolam.

Capture and transport are essential procedures for the management and conservation of southern white rhinoceroses (Ceratotherium simum simum), but are associated with stress-induced morbidity and mortality. To improve conservation efforts, it is crucial to understand the pathophysiology of rhinoceros stress responses and investigate drug combinations that could reduce these responses. In this study we measured rhinoceros stress responses to capture and transport by quantifying hematological and immunological changes together with adrenal hormone concentrations. We investigated whether the potent anxiolytic drug midazolam was able to mitigate these responses compared to azaperone, which is more commonly used during rhinoceros transport. Twenty three wild white rhinoceros bulls were transported for 6 h (280 km) within the Kruger National Park for reasons unrelated to this study. Rhinoceroses were immobilized with either etorphine-azaperone (group A, n = 11) or etorphine-midazolam (group M, n = 12) intramuscularly by darting from a helicopter. Azaperone (group A) or midazolam (group M) were re-administered intramuscularly every 2 h during transport. Serial blood samples were collected at capture (TC), the start of transport (T0) and after 6 h of transport (T6). Changes in hematological and immunological variables over time and between groups were compared using general mixed models. Increases in plasma epinephrine and serum cortisol concentrations indicated that rhinoceroses mounted a stress response to capture and transport. Packed cell volume decreased from TC to T6 indicating that stress hemoconcentration occurred at TC. Neutrophils progressively increased and lymphocytes and eosinophils progressively decreased from T0 to T6, resulting in an increase in neutrophil to lymphocyte ratio; a characteristic leukocyte response to circulating glucocorticoids. A reduction in serum iron concentrations may suggest the mounting of an acute phase response. Rhinoceroses experienced a decrease in unsaturated fatty acids and an increase in lipid peroxidation products at capture and toward the end of transport indicating oxidative stress. Midazolam, at the dose used in this study, was not able to mitigate adrenal responses to stress and appeared to directly influence leukocyte responses.

Intranasal epinephrine in dogs: Pharmacokinetic and heart rate effects.

Epinephrine is the standard of care for the treatment of severe allergy and anaphylaxis. Epinephrine is most often administered through the intramuscular (IM) route via autoinjector. The current study aimed to evaluate an alternative method of epinephrine treatment through intranasal (IN) delivery in dogs. The pharmacokinetic (PK) parameters of maximum plasma concentration (Cmax), time to reach maximum plasma concentration (Tmax), and area under the plasma concentration‐time curve from 0 to 90 minutes (AUC0–90) were observed after IN epinephrine (2, 3, 4, 5, 10, and 20 mg) and IM epinephrine via autoinjector (0.15 and 0.3 mg) for 90 minutes. Heart rate effects were measured after IN (2 and 5 mg) and IM (0.15 and 0.3 mg) epinephrine administration. IN epinephrine (5 mg) demonstrated significantly greater plasma epinephrine concentration at 1 minute as compared with IM epinephrine (0.3 mg) (1.68 ± 0.65 ng/mL vs 0.21 ± 0.08 ng/mL, P = .03). There were no significant differences in Cmax, Tmax, and AUC0–90 between 2‐mg IN and 0.15‐mg IM epinephrine or between 5‐mg IN and 0.3‐mg IM epinephrine. IN epinephrine reduced heart rate increases, as compared to IM epinephrine. IN and IM epinephrine were both well‐tolerated. Overall, IN epinephrine demonstrated advantages over IM epinephrine, including the rapid increase in plasma epinephrine and lack of increased heart rate over time.

Alleviation of cardiac mitochondrial dysfunction and oxidative stress underlies the protective effect of vitamin D in chronic stress-induced cardiac dysfunction in rats.

Chronic stress is associated with oxidative stress and mitochondrial dysfunction. These mechanisms promote adverse cardiovascular events. Though many experimental studies have reported a protective effect of vitamin D (VitD) on cardiovascular system, its effect on cardiovascular system in case of chronic stress is not studied yet. The present study aimed to detect the effects of VitD treatment against chronic immobilization stress (CIS)-induced cardiac dysfunction, focusing mainly on mitochondrial function and oxidative stress in rats. CIS showed cardiac dysfunction as indicated by a significant decrease in the left ventricular end-diastolic and systolic diameters and decrease in ejection fraction and fractional shortening compared to the control group. This was accompanied by a significant decrease in tissue reserves of reduced glutathione (GSH), superoxide dismutase (SOD), ATP and cardiolipin as well as increase in malondialdehyde (MDA) and expression of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α). All these effects were accompanied by a significant increase in plasma adrenaline and noradrenaline. Treatment with VitD ameliorated all the aforementioned CIS-induced effects except PGC-1α expression in a dose-dependent manner. To our knowledge, this is the first study describing the prophylactic cardioprotective effects of VitD against CIS by targeting mitochondrial function.

Effects of Caffeine on Physical and Cognitive Performance: A Brief Review

Caffeine is one of the most extensively studied and widely used ergogenic aid capable of improving many aspects of sport performance and cognitive abilities [1-12]. Some of the acute effects of caffeine supplementation are increases anaerobic power output and performance, increased muscular strength, endurance, and power, improvements to aerobic endurance, reduced fatigue, decreased RPE and pain, increased voluntary workload, and increased alertness [1-8]. Chronic caffeine consumption has also been shown to have a positive effect on long term memory, locomotor improvements, and overall mood state [9-11]. Some of the positive effects of athletic performance attributed to caffeine ingestion can be explained by its ability to moderate insulin sensitivity, increase plasma free fatty acids (FFAs), and increase plasma epinephrine [12].

Noradrenergic Activity in the Human Brain: A Mechanism Supporting the Defense Against Hypoglycemia.

Hypoglycemia, one of the major factors limiting optimal glycemic control in insulin-treated patients with diabetes, elicits a brain response to restore normoglycemia by activating counterregulation. Animal data indicate that local release of norepinephrine (NE) in the hypothalamus is important for triggering hypoglycemia-induced counterregulatory (CR) hormonal responses. To examine the potential role of brain noradrenergic (NA) activation in humans during hypoglycemia. A hyperinsulinemic-hypoglycemic clamp was performed in conjunction with positron emission tomographic imaging. Nine lean healthy volunteers were studied during the hyperinsulinemic-hypoglycemic clamp. Participants received intravenous injections of (S,S)-[11C]O-methylreboxetine ([11C]MRB), a highly selective NE transporter (NET) ligand, at baseline and during hypoglycemia. Hypoglycemia increased plasma epinephrine, glucagon, cortisol, and growth hormone and decreased [11C]MRB binding potential (BPND) by 24% ± 12% in the raphe nucleus (P < 0.01). In contrast, changes in [11C]MRB BPND in the hypothalamus positively correlated with increments in epinephrine and glucagon levels and negatively correlated with glucose infusion rate (all P < 0.05). Furthermore, in rat hypothalamus studies, hypoglycemia induced NET translocation from the cytosol to the plasma membrane. Insulin-induced hypoglycemia initiated a complex brain NA response in humans. Raphe nuclei, a region involved in regulating autonomic output, motor activity, and hunger, had increased NA activity, whereas the hypothalamus showed a NET-binding pattern that was associated with the individual's CR response magnitude. These findings suggest that NA output most likely is important for modulating brain responses to hypoglycemia in humans.

Changes in oxidized LDL during a half marathon in athletes with spinal cord injuries

Introduction:We reported previously that exercise significantly increases plasma adrenaline and oxidized low-density lipoprotein (oxLDL) in healthy subjects but not in persons with spinal cord injury (SCI). Since oxLDL and adrenaline levels are associated with oxidant/antioxidant balance, and exercise training elicits production of reactive oxygen species, we elucidated the effects of exercise on adrenaline, oxidant/antioxidant balance and oxLDL in individuals with SCI.Case Presentation:Eight subjects with cervical spinal cord injury (CSCI) and nine subjects with lower lesion of SCI (lower SCI (LSCI)) participated in a wheelchair half marathon race, and blood samples were collected before (pre), immediately after (post) and 1 h after the race (post 1 h). The blood samples were used to determine adrenaline, derivatives of reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP), both as markers for oxidant/antioxidant balance.Discussion:Pre-serum oxLDL levels were 147.2±8.1 and 97.0±10.4 U l−1 (mean±s.e.m.) in LCSI and CSCI subjects, respectively, and remained stable throughout the study. Adrenaline levels were higher in LSCI athletes than in CSCI athletes, especially post half marathon. Serum d-ROMs level did not change between pre and post in both groups. The mean BAP was significantly higher in LSCI than in CSCI subjects (2574±94.6 vs 2118±94.6 μmol l−1) at post, whereas the oxidative stress index (d-ROMs/BAP) was similar in the two groups throughout the study. In conclusion, exercise did not increase the d-ROMs or d-ROMs/BAP ratio in CSCI and LSCI subjects. The lack of increase in the plasma oxLDL level in SCI subjects was not due to the lack of response of adrenaline to exercise.

Clonidine as vasoconstrictor with lignocaine for intraoral anaesthesia in patients with hypertension

Background: Local block anaesthesia achieved with an adrenaline containing solution can lead to an increase in plasma adrenaline with significant and non-significant cardiovascular changes. Clinical studies have suggested that clonidine might have haemodynamic advantages over adrenaline as a vasoconstrictor because of its central hypotensive effect. Objectives: The objectives of this study is to evaluate the efficacy of clonidine as vasoconstrictor, to check any changes in haemodynamic parameters and also to find out the onset, duration, intensity of local anaesthesia. Methods: Study included 280 patients of ASA II group, aged 40–70 years, for extraction of mandibular teeth. Patients received 2 mL of 2% lidocaine with clonidine in concentration of 15 mg/mL. Systolic blood pressure, diastolic blood pressure, mean arterial pressure, heart rate, were recorded before, during, 5 min after administration of anaesthesia, during extraction, and 10 min after extraction. Findings: One way repeated measure analysis of variance was done using SPSS Vs 20. There is a significant difference in the haemodynamic parameters during different duration of anaesthesia. Conclusion: Clonidine when used with lignocaine as vasoconstrictor for intraoral anaesthesia in hypertensive patients brought about a reduction in the blood pressure retaining all the properties of lignocaine.

Mouth rinsing with a carbohydrate solution attenuates exercise-induced decline in executive function

BackgroundA decline in executive function could have a negative influence on the control of actions in dynamic situations, such as sports activities. Mouth rinsing with a carbohydrate solution could serve as an effective treatment for preserving the executive function in exercise. The purpose of this study was to examine the effects of mouth rinsing with a carbohydrate solution on executive function after sustained moderately high-intensity exercise.MethodsEight young healthy participants completed 65 min of running at 75% V̇O2max with two mouth-rinsing conditions: with a carbohydrate solution (CHO) or with water (CON). Executive function was assessed before and after exercise by using the incongruent task of the Stroop Color and Word Test. The levels of blood glucose; and plasma adrenocorticotropic hormone (ACTH), epinephrine, and norepinephrine (NE) were evaluated. A two-way repeated-measures ANOVA, with condition (CHO and CON) and time (pre-exercise and post-exercise) as factors, was used to examine the main and interaction effects on the outcome measures.ResultsThe reaction time in the incongruent condition of the Stroop test significantly increased after exercise in CON (pre-exercise 529 ± 45 ms vs. post-exercise 547 ± 60 ms, P = 0.029) but not in CHO (pre-exercise 531 ± 54 ms vs. post-exercise 522 ± 80 ms), which resulted in a significant interaction (condition × time) on the reaction time (P = 0.028). The increased reaction time in CON indicates a decline in the executive function, which was attenuated in CHO. Increases in plasma epinephrine and NE levels demonstrated a trend toward attenuation accompanying CHO (P < 0.085), which appeared to be associated with the preservation of executive function. The blood glucose concentration showed neither significant interactions nor main effects of condition.ConclusionsThese findings indicate that mouth rinsing with a carbohydrate solution attenuated the decline in executive function induced by sustained moderately high-intensity exercise, and that such attenuation seems to be unrelated to carbohydrate metabolic pathway but rather attributed, in part, to the inhibition of the excessive release of stress hormones.