Plasma Epinephrine Levels Research Articles

Orexin Receptor-1 in the Rostral Ventrolateral Medulla Mediates the Antihypertensive Effects of Electroacupuncture.

Electroacupuncture (EA) has been used to treat numerous diseases, including hypertension. This study aimed to investigate the long-term effect and underlying mechanisms of EA stimulation at the LI11 point on the hypertension and sympathetic nerve activity in two-kidney, one-clip (2K1C) hypertensive rats. EA (0.1–0.4 mA, 2 and 15 Hz) was applied to the acupoints LI11 overlying the deep radial nerve once a day for 6 weeks. The mean arterial pressure (MAP) and heart rate (HR) were determined by radiotelemetry, and the sympathetic nerve activity was evaluated by telemetric analyses of the low-frequency component of blood pressure (BP) and by plasma epinephrine and norepinephrine levels. The results showed 6 weeks of EA significantly lowered the increased BP effectively, inhibited the enhanced sympathetic nerve activities and attenuated cardiac hypertrophy in 2K1C hypertensive rats. The level of orexin receptor-1 (OX1R) in the rostral ventrolateral medulla (RVLM) after EA treatment was markedly reduced in 2K1C rats, while there was no difference in the RVLM expression of orexin receptor-2 (OX2R) in 2K1C and 2K1C+EA rats. Moreover, the increased pressor and depressor responses to microinjection of orexin A or OX1R antagonist SB408124 into the RVLM of 2K1C rats were significantly blunted by the EA treatment. These findings suggest that BP-lowering effect of EA on renovascular hypertension may be through inhibition of central sympathetic activities and modulation of functional orexin receptors in the RVLM.

Adrenal Aging and Its Implications on Stress Responsiveness in Humans.

Normal aging results in subtle changes both in ACTH and cortisol secretion. Most notable is the general increase in mean daily serum cortisol levels in the elderly, without a noteworthy alteration in the normal circadian rhythm pattern. Glucocorticoid excess seen in the elderly population can have serious consequences in both the structural and functional integrity of various key areas in the brain, including the hippocampus, amygdala, prefrontal cortex, with consequent impairment in normal memory, cognitive function, and sleep cycles. The chronically elevated glucocorticoid levels also impinge on the normal stress response in the elderly, leading to an impaired ability to recover from stressful stimuli. In addition to the effects on the brain, glucocorticoid excess is associated with other age-related changes, including loss of muscle mass, hypertension, osteopenia, visceral obesity, and diabetes, among others. In contrast to the increase in glucocorticoid levels, other adrenocortical hormones, particularly serum aldosterone and DHEA (the precursor to androgens and estrogens) show significant decreases in the elderly. The underlying mechanisms for their decrease remain unclear. While the adrenomedullary hormone, norephinephrine, shows an increase in plasma levels, associated with a decrease in clearance, no notable changes observed in plasma epinephrine levels in the elderly. The multiplicity and complexity of the adrenal hormone changes observed throughout the normal aging process, suggests that age-related alterations in cellular growth, differentiation, and senescence specific to the adrenal gland must also be considered.

The influence of a hot environment on physiological stress responses in exercise until exhaustion.

Exhaustive exercise in a hot environment can impair performance. Higher epinephrine plasma levels occur during exercise in heat, indicating greater sympathetic activity. This study examined the influence of exercise in the heat on stress levels. Nine young healthy men performed a maximal progressive test on a cycle ergometer at two different environmental conditions: hot (40°C) and normal (22°C), both between 40% and 50% relative humidity. Venous blood and saliva samples were collected pre-test and post-test. Before exercise there were no significant changes in salivary biomarkers (salivary IgA: p = 0.12; α-amylase: p = 0.66; cortisol: p = 0.95; nitric oxide: p = 0.13; total proteins: p = 0.07) or blood lactate (p = 0.14) between the two thermal environments. Following exercise, there were significant increases in all variables (salivary IgA 22°C: p = 0.04, 40°C: p = 0.0002; α-amylase 22°C: p = 0.0002, 40°C: p = 0.0002; cortisol 22°C: p = 0.02, 40°C: p = 0.0002; nitric oxide 22°C: p = 0.0005, 40°C: p = 0.0003, total proteins 22°C: p<0.0001, 40°C: p<0.0001 and; blood lactate 22°C: p<0.0001, 40°C: p<0.0001) both at 22°C and 40°C. There was no significant adjustment regarding IgA levels between the two thermal environments (p = 0.74), however the levels of α-amylase (p = 0.02), cortisol (p<0.0001), nitric oxide (p = 0.02) and total proteins (p = 0.01) in saliva were higher in the hotter conditions. Blood lactate was lower under the hot environment (p = 0.01). In conclusion, enduring hot temperature intensified stressful responses elicited by exercise. This study advocates that hot temperature deteriorates exercise performance under exhaustive stress and effort conditions.

Fear stress enhanced xenograft pancreatic tumor growth through activating epithelial-mesenchymal transition

ObjectiveCancer patients often experience multiple emotional distresses, particularly the fear of death. However, there are rare studies to assess the direct effect of the fear of death on disease progression. MethodsXenograft pancreatic cancer animal models were established in nude mice. Fear stress was induced to tumor bearing mice by closely housing with a cat and depressive behaviors were measured using open field test, forced swimming test, and sucrose consumption test. Plasma adrenaline concentration was measured using ELISA. ResultsFear stress induced depression-like behaviors in tumor bearing mice which were accompanied with increases in tumor growth, plasma adrenaline levels as well as the protein expression of alpha 2 adrenergic receptor (α2 AR) and beta 2 adrenergic receptor (β2-AR) in tumor tissues. The β-adrenergic antagonist propranolol (Pro) treatment blocked the effect of stress on tumor growth in pancreatic cancer xenograft animal model, but had no effects on the levels of plasma adrenaline level, and α2 AR and β2-AR expression in tumor tissues. Moreover, fear stress increased Frizzled-1, Wnt1, vimentin, but decreased E-cadherin protein expression in tumor tissues, while Pro reversed the effects of fear stress on the expression of these proteins. ConclusionFear of death impacted the growth of PDAC tumor though activation of epithelial-mesenchymal transition. Treating pancreatic cancer patients with β-adrenergic antagonist implicates an effective strategy to treat cancer including PDAC.

Ivabradine reduces baseline and stress-induced increase of heart rate and blood pressure and modulates neuroendocrine stress response in rats depending on stressor intensity.

Ivabradine, a selective inhibitor of the sinoatrial pacemaker, is used in clinical practice to reduce heart rate. However, its potential effect on the neuroendocrine stress response has not been investigated. Therefore, we determined the effect of administering ivabradine to rats on cardiovascular parameters and plasma levels of epinephrine, norepinephrine, and corticosterone. Ivabradine was administered intraperitoneally 30 min before exposing animals to either handling, restraint, or immobilization stress. Heart rate and blood pressure were monitored telemetrically. Blood samples were collected before, during, and after stressor exposure to determine the extent of the neuroendocrine stress response as reflected by plasma epinephrine, norepinephrine, and corticosterone levels. In animals pretreated with ivabradine, significantly lower values of heart rate and blood pressure were found during both the baseline period and during exposure to stressors, as well as during the rest period following stressor exposure. Ivabradine also significantly reduced handling-induced epinephrine and norepinephrine release into the bloodstream. However, ivabradine significantly potentiated restraint- and immobilization-induced increases of plasma epinephrine levels, whereas stress-induced changes in plasma norepinephrine and corticosterone levels were ambiguous. Our data shows that ivabradine significantly reduces blood pressure in rats during both baseline and stressful conditions, and also affects the neuroendocrine stress response. These findings show that viscerosensory signaling from the cardiovascular system may significantly modulate the neuroendocrine stress response.

The Effects of Tryptophan Enhancement and Depletion on Plasma Catecholamine Levels in Healthy Individuals.

Central nervous system (CNS) serotonin (5-HT) exerts both excitatory and inhibitory effects on the sympathetic nervous system (SNS) in animals. In this study, we examine the effects of tryptophan enhancement and depletion on plasma catecholamine levels in humans. The total sample consisted of 164 healthy men and women who were tested for 2 days. Seventy-nine participants were randomized to a tryptophan enhancement condition and 85 to a tryptophan depletion condition. Both protocols consisted of a "sham day," followed by an "active day." Blood samples for assessment of plasma norepinephrine and epinephrine levels were collected before and after tryptophan enhancement/depletion. Data were analyzed using general linear models. Separate analyses were conducted for each study arm and for each measure. In the depletion condition, both epinephrine (F(5,330) = 2.69, p = .021) and norepinephrine (F(5,335) = 2.79, p = .018) showed small increases on active versus "sham" depletion days. There were also significant day by time interactions for epinephrine (F(3,171) = 39.32, p < .0001) and norepinephrine (F(3,195) = 31.09, p < .0001) levels in the enhancement arm. Tryptophan infusion resulted in a marked increase in epinephrine (Premean = 23.92 (12.23) versus Postmean = 81.57 (62.36)) and decrease in norepinephrine (Premean = 257.2 (106.11) versus Postmean = 177.04 (87.15)), whereas levels of both catecholamines were stable on the "sham day." CNS 5-HT exerts both inhibitory and excitatory effects on SNS activity in humans, potentially due to stimulation of CNS 5-HT receptors that have shown to have inhibitory (5-HT1A) and excitatory (5-HT1A and/or 5-HT2) SNS effects in animal models.

Greater early epinephrine rise with head-up posture: A marker of increased syncope susceptibility in vasovagal fainters.

Head-up tilt (HUT) is widely used for diagnostic evaluation of patients with suspected vasovagal syncope (VVS), but also offers an opportunity to study VVS pathophysiology. In this regard, it is known that plasma epinephrine (Epi) levels and Epi/norepinephrine (NE) ratio are markedly increased from baseline at the time of HUT-induced VVS. However, whether these changes contribute to VVS susceptibility remains uncertain. We hypothesized that if catecholamines contributed to VVS directly, then a greater increase of plasma Epi and Epi/NE ratio early during HUT would be associated with shorter time to syncope. The patient population comprised 33 individuals (14 men, 43 ± 2 years) with suspected VVS in whom 70° HUT reproduced symptoms. Arterial Epi and NE concentrations were collected at baseline (supine) and 2 minutes of HUT. Linear, exponential, and multiple regression were used to access the association between changing catecholamine levels and time to syncope. Mean ± SD time to positive HUT was 11 (7.6) minutes. Higher plasma Epi levels (pg/mL) both at baseline and at 2 minutes upright correlated with shorter time to syncope (baseline, R = -0.35, P = 0.048; and 2 minutes, R = -0.58, P = 0.001). Similarly, a greater Epi/NE ratio at 2 minutes head-up correlated with earlier time to syncope (R = -0.49, P = 0.007). These relationships remained significant after adjusting for age and sex (P = 0.006 and 0.02, respectively). Greater Epi levels and Epi/NE ratio early during HUT were associated with shorter time to VVS, suggesting a possible contribution to VVS susceptibility.

Plasma Epinephrine Level and its Causal Link to Takotsubo Syndrome Revisited: Critical Review with a Diverse Conclusion.

Takotsubo syndrome (TS) is a recognized acute cardiac syndrome with a clinical presentation resembling that of an acute coronary syndrome (ACS). The defining feature of TS is the reversible left ventricular wall motion abnormality (LVWMA), which has a unique circumferential pattern resulting in a conspicuous ballooning of the left ventricle during systole, and extending beyond the coronary artery supply territory. The pathogenesis of TS is still elusive and several pathophysiological mechanisms have been proposed. A common portrayal of the syndrome in the literature is that the disease is characterized by massive surge of plasma catecholamines including epinephrine. Based on the assumption of massive plasma epinephrine elevation, some investigators hypothesized that the circulatory plasma epinephrine plays a pivotal role in the pathogenesis of TS. One typical such hypothesis is epinephrine induced switch in signal trafficking causing apical or mid-apical ballooning in TS. In-depth analysis of the literature reveals that no study with certainty has shown "massive" plasma epinephrine elevations in TS. Furthermore, the literature evidences challenging the epinephrine-induced switch in signal trafficking are substantial. In this review, sufficient data, indicating that the plasma epinephrine in TS is either normal or moderately elevated in all studies, are provided. Noteworthy, epinephrine may act as a trigger factor for TS-induction but there is no evidence for a direct causal link between epinephrine and TS.

PL-010 Chronic mild stress improves glucose homeostasis via myonectin-mediated suppression of sympathetic activity in high-fat diet-fed mice

Objective Recent studies suggest that chronic stress exposure can ameliorate the progression of diet-induced prediabetic disease, by inhibiting an increase in weight gain, caloric intake and efficiency and insulin resistance. To determine the underlying mechanism by which chronic stress improves the progression of type 2 diabetes, we developed a model of chronic mild stress in high-fat diet(HFD)-fed mice which are resistant to obesity and exhibit a healthy-like metabolic phenotype.&#x0D; Methods High-fat diet (HFD): 45% kcal derived from fat (Research Diets, Inc.).Mice experienced one stressor during the day and a different stressor during the night. Stressors were randomly chosen from the following list : cage tilt on a 45° angle for 1 to 16 h; food deprivation for 12 to 16 h; white noise for 1 to 16 h; strobe light illumination for 1 to 16 h; crowded housing; light cycle (continuous illumination) for 24 to 36 h; dark cycle (continuous darkness) for 24 to 36 h; water deprivation for 12 to 16 h; damp bedding (200 ml water poured into sawdust bedding) for 12 to 16 h.Recombinant adeno-associated virus (AAV): AAV9 vectors encoding myonectin under the control of the ubiquitous CMV promoter (AAV9-CMV-Vip) or an equal dose of the AAV9-CMV-null vector were delivered to C57BL/6 mice by the tail vein. Mice were deprived of food for 16 h and then subjected to test 7 days after AAV injection.&#x0D; Results Chronic stress improved glucose intolerance and sympathetic overactivity in HFD-fed mice. Chronic stress attenuated epinephrine(EPI)-stimulated glycerol release into blood in vivo and accelerated glycerol release from white adipose tissue followed by in vitro incubation with EPI. Chronic stress reduced plasma triglyceride but increased the levels of plasma insulin and myonectin. We further found that adeno-associated virus 9 (AAV9)-mediated myonectin overexpression improved glucose homeostasis and reduced epinephrine sensitivity. Myonectin overexpression reduced plasma norepinephrine, EPI and leptin levels, and increased insulin sensitivity in brown and white adipose tissue. Intense sympathetic activity with high-intensity running inhibited myonectin expression in skeletal muscle, whereas medium and low-intensity exercise running increased myonectin expression.&#x0D; Conclusions These findings suggest that chronic mild stress can improve glucose homeostasis via myonectin-mediated suppression of sympathetic activity in high-fat diet-fed mice.

Association Between Cardiovascular Risk Factors and Stress Hormones With Cognitive Performance in Mexican Adolescents.

The objective of this study was to determine whether cardiovascular disease (CVD) risk factors and stress hormones are associated with cognitive performance in Mexican adolescents. This was a cross-sectional study including 139 Mexican adolescents 10-14 years old. Participants were divided into three categories: 0, 1-2, and ≥3 CVD risk factors. These factors included: high-density lipoprotein-cholesterol (HDL-C) <40 mg/dl; waist circumference (WC) ≥90th percentile for age and sex, systolic or diastolic blood pressure ≥90th percentile for age, sex, and height; and triacylglycerols (TGs) ≥110 mg/dl. Low-density lipoprotein-cholesterol (LDL-C), very low-density lipoprotein-cholesterol (VLDL-C), total cholesterol, cortisol, and plasma catecholamines were measured as well. Furthermore, attention, memory, and executive functions were evaluated using a validated test for Spanish-speaking individuals (Neuropsi). Adolescents in the three risk categories did not show significant differences in Neuropsi test performance tasks; however, they presented different lipid and plasma norepinephrine concentrations. TG and VLDL-C were inversely associated with memory (r = -0.19, **p < .01). Multivariate regression analysis showed consistently that TG/HDL-C ratio was inversely related to attention-memory general score (standardized β = -0.99, t = -2.30, p = .023), memory (standardized β = -0.83, t = -2.08, p = .039), and attention-executive functions (standardized β = -1.02, t = -2.42, p = .017). Plasma epinephrine levels presented an inverse and weak relation to the attention-executive functions score (standardized β = -0.18, t = -2.19, p = .030). Cognitive performance is not completely dependent on the accumulation of risk factors, but instead on the combination of strong predictors of CVD like waist to height ratio, TG/HDL-C, and VLDL-C. Plasma norepinephrine and epinephrine have a stronger association with cognition and CVD risk than dopamine and cortisol.

Circulating catecholamines are associated with biobehavioral factors and anxiety symptoms in head and neck cancer patients.

Studies have shown that stress-related catecholamines may affect cancer progression. However, little is known about catecholamine secretion profiles in head and neck cancer patients. The present study investigated plasma norepinephrine and epinephrine levels in head and neck squamous cell carcinoma (HNSCC) patients and patients with oral leukoplakia, as well as their association with clinicopathological and biobehavioral variables and anxiety symptoms. A total of 93 patients with HNSCC and 32 patients with oral leukoplakia were included. Plasma norepinephrine and epinephrine levels were measured by high performance liquid chromatography with electrochemical detection (HPLC-ED), and psychological anxiety levels were measured by the Beck Anxiety Inventory (BAI). Plasma norepinephrine and epinephrine concentrations were significantly higher in patients with oral and oropharyngeal squamous cell carcinoma (SCC) compared to non-cancer patients. Oral SCC patients displayed plasma norepinephrine levels about six times higher than oropharyngeal SCC patients, and nine times higher than oral leukoplakia patients (p < .001). Plasma epinephrine levels in oral SCC patients were higher compared to the oropharyngeal SCC (p = .0097) and leukoplakia (p < .0001) patients. Oropharyngeal SCC patients had higher plasma norepinephrine (p = .0382) and epinephrine levels (p = .045) than patients with oral leukoplakia. Multiple regression analyses showed that a history of high alcohol consumption was predictive for reduced plasma norepinephrine levels in the oral SCC group (p < .001). Anxiety symptom of “hand tremor” measured by the BAI was an independent predictor for higher plasma norepinephrine levels in HNSCC patients (β = 157.5, p = .0377), while the “heart pounding/racing” symptom was independently associated with higher plasma epinephrine levels in the oropharyngeal SCC group (β = 15.8, p = .0441). In oral leukoplakia patients, sleep deprivation and worse sleep quality were independent predictors for higher plasma norepinephrine levels, while severe tobacco consumption and higher anxiety levels were factors for higher plasma epinephrine levels. These findings suggest that head and neck cancer patients display sympathetic nervous system hyperactivity, and that changes in circulating catecholamines may be associated with alcohol consumption, as well as withdrawal-related anxiety symptoms.

Relationship between sympathoadrenal and pituitary-adrenal response during colorectal distention in the presence of corticotropin-releasing hormone in patients with irritable bowel syndrome and healthy controls.

Corticotropin-releasing hormone (CRH) mediates stress responses in the brain-gut axis. Administration of CRH modulates brain activation, for example by controlling the autonomic nervous system in response to colorectal distention. Here, we investigated the relationship between sympathoadrenal and hypothalamic-pituitary-adrenal (HPA) responses to colorectal distention in patients with irritable bowel syndrome (IBS). We enrolled 32 patients with IBS (16 women and 16 men) and 32 healthy subjects (16 women and 16 men), and randomly divided them between CRH and saline injection groups. The patients randomly underwent no (0 mmHg), mild (20 mmHg), or strong (40 mmHg) colorectal distension. CRH (2 μg/kg) or saline was then administered via injection, and the distention protocol was repeated. The heart rate (HR) and HR variability (HRV; calculated as the low [LF] to high frequency [HF] peak ratio, LF/HF) were analyzed using electrocardiography. Plasma noradrenaline, adrenaline, adrenocorticotropic hormone (ACTH), and cortisol levels were measured at the time of each distention. Plasma adrenaline levels were shown to be associated with plasma ACTH levels in HCs injected with CRH during distention using structural equation modeling analysis. Patients with IBS injected with placebo during distention displayed a closer association between these two parameters than those injected with CRH. Generalized estimating equation analysis revealed a significant distention × group × drug interaction for HF power. Moreover, there was a strong correlation between adrenaline and HRV upon CRH injection in controls, but not patients with IBS. The relationship between HPA-sympathoadrenal responses and CRH levels during colorectal distention differs between patients with IBS and controls. Modulation of adrenal gland activity in response to ACTH stimulation may contribute to the brain-gut pathophysiology characteristic of IBS.

Metabolic stress-dependent regulation of the mitochondrial biogenic molecular response to high-intensity exercise in human skeletal muscle.

Low-volume high-intensity exercise training promotes muscle mitochondrial adaptations that resemble those associated with high-volume moderate-intensity exercise training. These training-induced mitochondrial adaptations stem from the cumulative effects of transient transcriptional responses to each acute exercise bout. However, whether metabolic stress is a key mediator of the acute molecular responses to high-intensity exercise is still incompletely understood. Here we show that, by comparing different work-matched low-volume high-intensity exercise protocols, more marked metabolic perturbations were associated with enhanced mitochondrial biogenesis-related muscle mRNA responses. Furthermore, when compared with high-volume moderate-intensity exercise, only the low-volume high-intensity exercise eliciting severe metabolic stress compensated for reduced exercise volume in the induction of mitochondrial biogenic mRNA responses. The present results, besides improving our understanding of the mechanisms mediating exercise-induced mitochondrial biogenesis, may have implications for applied and clinical research that adopts exercise as a means to increase muscle mitochondrial content and function in healthy or diseased individuals. The aim of the present study was to examine the impact of exercise-induced metabolic stress on regulation of the molecular responses promoting skeletal muscle mitochondrial biogenesis. Twelve endurance-trained men performed three cycling exercise protocols characterized by different metabolic profiles in a randomized, counter-balanced order. Specifically, two work-matched low-volume supramaximal-intensity intermittent regimes, consisting of repeated-sprint (RS) and speed endurance (SE) exercise, were employed and compared with a high-volume continuous moderate-intensity exercise (CM) protocol. Vastus lateralis muscle samples were obtained before, immediately after, and 3h after exercise. SE produced the most marked metabolic perturbations as evidenced by the greatest changes in muscle lactate and pH, concomitantly with higher post-exercise plasma adrenaline levels in comparison with RS and CM. Exercise-induced phosphorylation of CaMKII and p38 MAPK was greater in SE than in RS and CM. The exercise-induced PGC-1α mRNA response was higher in SE and CM than in RS, with no difference between SE and CM. Muscle NRF-2, TFAM, MFN2, DRP1 and SOD2 mRNA content was elevated to the same extent by SE and CM, while RS had no effect on these mRNAs. The exercise-induced HSP72 mRNA response was larger in SE than in RS and CM. Thus, the present results suggest that, for a given exercise volume, the initial events associated with mitochondrial biogenesis are modulated by metabolic stress. In addition, high-intensity exercise seems to compensate for reduced exercise volume in the induction of mitochondrial biogenic molecular responses only when the intense exercise elicits marked metabolic perturbations.

MP09-09 BRAIN NITRIC OXIDE CAN INDUCE FREQUENT URINATION IN RATS

You have accessJournal of UrologyBladder & Urethra: Anatomy, Physiology & Pharmacology I1 Apr 2018MP09-09 BRAIN NITRIC OXIDE CAN INDUCE FREQUENT URINATION IN RATS Takahiro Shimizu, Hideaki Ono, Shogo Shimizu, Youichirou Higashi, Suo Zou, Masaki Yamamoto, Takaaki Aratake, Tomoya Hamada, Yoshiki Nagao, Yusuke Ueba, Masashi Honda, and Motoaki Saito Takahiro ShimizuTakahiro Shimizu More articles by this author , Hideaki OnoHideaki Ono More articles by this author , Shogo ShimizuShogo Shimizu More articles by this author , Youichirou HigashiYouichirou Higashi More articles by this author , Suo ZouSuo Zou More articles by this author , Masaki YamamotoMasaki Yamamoto More articles by this author , Takaaki AratakeTakaaki Aratake More articles by this author , Tomoya HamadaTomoya Hamada More articles by this author , Yoshiki NagaoYoshiki Nagao More articles by this author , Yusuke UebaYusuke Ueba More articles by this author , Masashi HondaMasashi Honda More articles by this author , and Motoaki SaitoMotoaki Saito More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.335AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Nitric oxide (NO) has a local inhibitory effect on urination. While in the central nervous system, NO seems to have both inhibitory and facilitatory effects on micturition. We previously reported that an NO donor SIN-1 centrally activated the sympatho-adrenomedullary (SA) system in rats. In this study, we investigated effects of centrally administered SIN-1 on micturition and their dependence on the SA system in rats. METHODS Urethane anesthetized (0.8-1.0 g/kg, ip) male Wistar rats (300-400 g) were used. (1) Catheters were inserted into the bladder and the femoral artery in order to perform continuous cystometrograms (CMG, 12 ml/h saline infusion) and to collect blood samples, respectively. Three hours after the surgery, SIN-1 (100 or 250 μg/rat) or vehicle was icv administered. Saline infusion into the bladder was started 1 hour before the icv administration. Plasma noradrenaline (NA) and adrenaline (Ad) levels were measured at 5 min after the icv administration. In some experiments, carboxy-PTIO (PTIO, an NO scavenger, 750 μg/rat) was icv pretreated 30 min before icv SIN-1 administration. (2) Three hours after the surgery of a bladder catheter insertion, single CMG (12 ml/h saline infusion) was performed. After 4-5 times of single CMG, SIN-1 (250 μg/rat) was icv administered, then single CMG was continued for 1 hour. RESULTS (1) SIN-1 dose-dependently reduced intercontraction intervals (ICI) and elevated plasma Ad without altering maximal voiding pressure or plasma NA (Tables 1-2). An insufficient dose of SIN-1 (100 μg/rat) for elevating plasma AD could induce ICI reduction (Tables 1-2). These SIN-1-induced responses were inhibited by PTIO (Table 3). (2) SIN-1 reduced single-voided volume (Vv) and bladder capacity (BC) without altering post-voiding residual urine volume or voiding efficiency (Table 4). CONCLUSIONS NO centrally induces frequent urination shown by reduced ICI, Vv and BC, independent of the central SA outflow. Thus, the brain nitrergic pathway that is directly involved in the control of micturition could be a new target for the treatment of bladder dysfunction. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e109 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Takahiro Shimizu More articles by this author Hideaki Ono More articles by this author Shogo Shimizu More articles by this author Youichirou Higashi More articles by this author Suo Zou More articles by this author Masaki Yamamoto More articles by this author Takaaki Aratake More articles by this author Tomoya Hamada More articles by this author Yoshiki Nagao More articles by this author Yusuke Ueba More articles by this author Masashi Honda More articles by this author Motoaki Saito More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Biological Response to Stress During Battlefield Trauma Training: Live Tissue Versus High-Fidelity Patient Simulator.

Tactical Combat Casualty Care (TCCC) training imposes psychophysiological stress on medics. It is unclear whether these stress levels vary with the training modalities selected. It is also unclear how stress levels could have an impact on medical performance and skill uptake. We conducted a pilot study to compare the effects of live tissue (LT) with a high-fidelity patient simulator (SIM) on the level of stress elicited, performance, and skill uptake during battlefield trauma training course in an operating room (OR) and in a simulated battlefield scenario (field). In the report, we studied the effects of training modalities and their changes on stress levels by measuring different biomarkers (salivary amylase, plasma catecholamines, and neuropeptide Y) at various time points during the trauma training course. We found that the training resulted in significant psychophysiological stress as indicated by elevated levels of various biomarkers relative to baseline immediately after both OR and field assessment (p < 0.05). Compared with pre-OR levels, the LT training in the OR resulted in significant increases in the plasma levels of epinephrine, norepinephrine, and neuropeptide (p = 0.013, 0.023, 0.004, respectively), whereas the SIM training in the OR resulted in significant increases in the plasma levels of norepinephrine and neuropeptide (p = 0.003 and 0.008). Compared with pre-field levels, we found significant increases in plasma epinephrine concentration in the SIM group (p = 0.016), plasma norepinephrine concentration in the LT group (p = 0.015), and plasma neuropeptide Y concentration in both LT (p = 0.006) and SIM groups (p = 0.029). No differences in the changes of biomarker levels were found between LT and SIM groups in the OR and field. Compared with pre-field levels, the testing on the same modality as that in the OR in the simulated battlefield resulted in significant increases in norepinephrine and neuropeptide levels (p = 0.013 and 0.015), whereas the testing on different modalities resulted in significant increases in amylase, epinephrine, and neuropeptide levels (p = 0.016, 0.05, 0.018, respectively). There was a significantly larger increase in plasma norepinephrine concentration (p = 0.031) and a trend toward a greater increase in the salivary amylase level (p = 0.052) when the field testing involved a different modality than the OR compared with when OR and field testing involved the same modality. Although most of the biomarkers returned to baseline levels after 24 h, plasma norepinephrine levels remained significantly higher regardless of whether field testing occurred on the same or different modality compared with OR (p = 0.040 and 0.002). TCCC training led to significant increase in psychophysiological stress, as indicated by elevated levels of various biomarkers. The training modalities did not result in any differences in stress levels, whereas the switch in training modalities appeared to elicit greater stress as evidenced by changes in specific biomarkers (amylase and norepinephrine). A comparative study with a larger sample size is warranted.

Abstract TP400: Acute Catecholamine Surge Reflects the Prognosis in Patients With Aneurysmal Subarachnoid Hemorrhage

Objective: We investigated that the characteristics of serum catecholamine concentration at the hyper-acute phase of aneurysmal subarachnoid hemorrhage (SAH) and its relationship between patient outcome and delayed vasospasm. Methods: Patients with aneurysmal SAH (n=170) were prospectively enrolled between 2008 and 2011. Baseline demographic data and physiological parameters, including plasma concentrations of adrenaline (AD), noradrenaline (NA) and dopamine (DP) were evaluated. Results: On admission, plasma AD, NA and DP levels were significantly higher in patients with a poor clinical grade on admission (Hunt and Kosnik: IV-V), compared to those with a good clinical grade on admission (Hunt and Kosnik: I-III). AD showed a significantly high concentration immediately after the onset of SAH and then rapidly decreased. The levels of NA peaked within 6 hours after onset, then significantly decreased. The time course of the elevation of DP showed a similar trend to that of NA. The each catecholamine levels significantly correlated with each other. Multivariate analyses demonstrated age, poor clinical grade, plasma AD and NA levels were predictors of poor patient outcome. Poor clinical grade, Fisher scale and plasma AD level were predictors of the development of delayed vasospasm. Conclusion: The present study suggests that sympathetic activation in patients in the acute phase of SAH reflects the severity of SAH, and is closely related to the development of delayed vasospasm, leading to the subsequent immune response and inflammatory reactions. Suppressing catecholamine surge in hyper-acute phase may contribute to prevention of vasospasm and improvement of patient outcome.

Does the anesthetic technique influence the epinephrine and norepinephrine concentration during pelvic surgery?

Background: Epinephrine and norepinephrine concentrations increase by up to ten-fold immediately after surgical injury depending on the severity of the injury. However, the plasma levels of epinephrine and norepinephrine do not necessarily increase concurrently. The plasma epinephrine levels increase for about 48 h, while the norepinephrine levels remain elevated for about 8-10 days after injury. The choice of anesthesia has been shown to influence the secretion of epinephrine and norepinephrine. Materials and Methods: We compared the effects of balanced combined spinal-epidural anesthesia (CSEA, n = 20) and general anesthesia relaxant (GAR, n = 20) on epinephrine and norepinephrine concentrations during major pelvic surgery in patients with uterine mass > 20 weeks gestation. Blood samples for epinephrine and norepinephrine were analyzed at preinduction and 1, 3, and 4 h after surgical incision using enzyme-linked immunosorbent assay technique. Results: The mean norepinephrine concentration differs significantly after incision; at 1 h, CSEA 230.11 ± 42.85 versus GAR 51.25 ± 29.15 pg/ml, P = 0.015; and at 3 h, CSEA 116.22 ± 39.91 versus GAR 27.00 ± 19.89 pg/ml, P = 0.045. The norepinephrine concentrations increased from preinduction values after incision; at 1 h, increased in CSEA by +168% but increased in GAR by +31.7%; at 3 h, increased in CSEA by +35.64% but decreased in GAR by -22.85%; while at 4 h, decreased in CSEA by −3.37% but increased in GAR by +38.94% , P = 0.04 [Figure 2]. The mean epinephrine was comparable during the study, P > 0.05, while the mean heart rate, mean arterial blood pressure, and estimated blood loss were significantly lower with CSEA. Conclusion: We have demonstrated that in patients with uterine mass >20 weeks gestation, CSEA when compared to general anesthesia resulted in an initial increase in mean norepinephrine concentration 1 h after surgical incision followed by gradual decrease toward preinduction values.

Effects of propranolol and clonidine on brain edema, blood-brain barrier permeability, and endothelial glycocalyx disruption after fluid percussion brain injury in the rat.

Traumatic brain injury causes a disruption of the vascular endothelial glycocalyx layer that is associated with an overactivation of the sympathoadrenal system. We hypothesized that early and unselective beta-blockade with propranolol alone or in combination with the alfa2-agonist clonidine would decrease brain edema, blood-brain barrier permeability, and glycocalyx disruption at 24 hours after trauma. We subjected 53 adult male Sprague-Dawley rats to lateral fluid percussion brain injury and randomized infusion with propranolol (n = 16), propranolol + clonidine (n = 16), vehicle (n = 16), or sham (n = 5) for 24 hours. Primary outcome was brain water content at 24 hours. Secondary outcomes were blood-brain barrier permeability and plasma levels of syndecan-1 (glycocalyx disruption), cell damage (histone-complexed DNA fragments), epinephrine, norepinephrine, and animal motor function. We found no difference in brain water content (mean ± SD) between propranolol (80.8 ± 0.3%; 95% confidence interval [CI], 80.7-81.0) and vehicle (81.1 ± 0.6%; 95% CI, 80.8-81.4) (p = 0.668) or between propranolol/clonidine (80.8 ± 0.3%; 95% CI, 80.7-81.0) and vehicle (p = 0.555). We found no effect of propranolol and propranolol/clonidine on blood-brain barrier permeability and animal motor scores. Unexpectedly, propranolol and propranolol/clonidine caused an increase in epinephrine and syndecan-1 levels. This study does not provide any support for unselective beta-blockade with propranolol or the combination of propranolol and the alfa2-agonist clonidine on brain water content. The novel finding of an increase in plasma concentrations of epinephrine and syndecan-1 after propranolol treatment in traumatic brain injury is of unclear significance and should be investigated further.

Plasma corticosterone, epinephrine, and norepinephrine levels increase during administration of nitrous oxide in rats

Nitrous oxide (N2O) is a gaseous drug with abuse potential. Despite its common clinical use, little is known about whether N2O administration activates the HPA axis and/or the sympathetic adrenomedullary system. The goal of this study was to determine whether 60% N2O alters plasma concentrations of corticosterone (CORT), epinephrine (EPI), and norepinephrine (NE) in male Long-Evans rats. A gas-tight swivel assembly in the lid of a gas administration chamber allowed the remote collection of blood samples from an indwelling jugular vein catheter at four time-points: baseline and at 30, 60, and 120 min during a two-hour administration of 60% N2O. Relative to baseline, plasma CORT (n = 9) was significantly elevated at all three time-points during N2O inhalation (mixed model analysis, p = .001) and plasma EPI and NE levels were each significantly elevated (n = 8, p ≤ .001) at the 30 min assessment. EPI then declined and did not differ from baseline at the 60 and 120 min assessments (p > .05) whereas NE remained elevated (120 min, p = .001). Administration of 60% N2O increases circulating CORT, EPI, and NE, supporting N2O as a physiological stressor. An N2O-induced increase in CORT is consistent with the observation that addictive drugs typically activate the HPA axis causing increased plasma levels of glucocorticoids. Allostatic models of drug addiction typically involve stress systems and the possible role of stress hormones in N2O-induced allostatic dysregulation is discussed.

β₂-Adrenoceptor Blockade Deteriorates Systemic Anaphylaxis by Enhancing Hyperpermeability in Anesthetized Mice.

PurposePatients treated with propranolol, a nonselective β-adrenoceptor antagonist, develop severe anaphylaxis, but the mechanism remains unknown. We determined effects of β1- and β2-adrenoceptor antagonists on the anaphylaxis-induced increase in vascular permeability in mice.MethodsIn anesthetized ovalbumin-sensitized C57BL mice, mean arterial blood pressure (MBP) was measured, and Evans blue dye extravasation and hematocrit (Hct) were assessed at 20 minutes after antigen injection. The following pretreatment groups (n=7/group) were studied: (1) sensitized control (non-pretreatment), (2) propranolol, (3) the selective β2-adrenoceptor antagonist ICI 118,551, (4) the selective β1-adrenoceptor antagonist atenolol, (5) adrenalectomy, (6) the selective β2-adrenoceptor agonist terbutaline, and (7) non-sensitized groups.ResultsThe antigen injection decreased MBP, and increased Hct and vascular permeability in the kidney, lung, mesentery, and intestine, but not in the liver or spleen. Pretreatment with ICI 118,551, propranolol and adrenalectomy, but not atenolol, reduced the survival rate and augmented the increases in Hct and vascular permeability in the kidney, intestine, and lung as compared with the sensitized control group. Pretreatment with terbutaline abolished the antigen-induced alterations. Plasma epinephrine levels were increased significantly in the sensitize control mice.ConclusionsBlockade of β2-adrenoceptor can deteriorate systemic anaphylaxis by augmenting hyperpermeability-induced increase in plasma extravasation by inhibiting beneficial effects of epinephrine released from the adrenal glands in anesthetized mice.