Sympathetic Nerve Stimulation Research Articles

B-AB01-04 INTERACTION BETWEEN ISCHEMIA AND SYMPATHETIC ACTIVITY ON CARDIAC ELECTROPHYSIOLOGY AND ARRHYTHMIA IN THE INNERVATED LANGENDORFF-PERFUSED MOUSE HEART

Sympathetic activation of the heart plays a key role in the modulation of cardiac electrophysiology and arrhythmogenesis. It is generally believed that sympathetic activation is proarrhythmic in the setting of cardiac ischemia. However, few studies have looked at the dynamic effects of physiological sympathetic nerve activation on cardiac electrophysiological activities during ischemia. To investigate the effects of sympathetic activation in the innervated Langendorff-perfused mouse heart subjected to acute ischemia. The heart and posterior thoracic cavity from mice (C57Bl6, N=4) were dissected and perfused through the descending aorta for dual optical mapping of transmembrane potential (Vm) and intracellular Ca2+ to study the effects of sympathetic nerve stimulation (SNS). SNS, achieved through spinal cord stimulation at T1-T3, was performed before, during and immediately after 5 min of low-flow ischemia (10% of pre-ischemic flow rate). Early afterdepolarizations (EADs) and ventricular tachycardia (VT) occurred in all 4 animals within 5 min of ischemia and immediately upon reperfusion. Both SNS and ventricular pacing, during either ischemia or reperfusion, completely abolished EADs and VT induced by global low-flow ischemia and reperfusion (Fig). In the isolated innervated mouse heart, we showed that sympathetic stimulation protects against ischemia-induced cardiac arrhythmias potentially by over-driving ventricular ectopic activity.

B-PO04-010 THE EFFECT OF CHRONIC NICOTINE EXPOSURE ON CARDIAC ELECTROPHYSIOLOGY IN THE RABBIT HEART

Tobacco smoke exposure is associated with increased risk for atrial and ventricular arrhythmias. However, the individual components of tobacco smoke that may promote arrhythmias and the underlying electrophysiological mechanisms responsible are unknown. Nicotine (NIC) is a major component of tobacco smoke and emerging tobacco products, including e-cigarettes. To determine the effects of chronic NIC exposure on autonomic and electrophysiological remodeling in the rabbit heart. Fully innervated hearts from rabbits exposed to NIC (21mg/day, transdermal patch, 28 days, n=7) or control (CT, n=4) rabbit hearts were optically mapped using voltage- (RH237) and calcium-sensitive (Rhod2-AM) indicators. Sympathetic nerve stimulation (SNS) was performed with electrical stimulation at the first thoracic vertebrae in which voltage was kept constant (7 V) and frequency was increased in 0.5 Hz increments until a 15% increase in heart rate (HR) was achieved. B-adrenergic (B-AR) responsiveness was evaluated with norepinephrine (500nM, NE). Baseline HR was higher in NIC vs. CT (215.8 BPM vs. 151 BPM, p<0.05). SNS stimulation thresholds necessary to produce an increase in HR were higher in NIC vs. CT (4.17 Hz vs. 1.38 Hz, p<0.05). Maximal HR increase after 40s of SNS trended lower in NIC vs. CT (19.38 vs. 54.30% increase, p=0.1). SNS also tended to produce a smaller change in action potential duration (APD80: -8.14 vs. -16.68% decrease, p=NS) and in calcium transient duration (CaTD80: -7.80 vs. - 20.74% decrease, p=NS) in NIC vs. CT. B-AR responsiveness was decreased in NIC vs. CT (33.38 vs. 75.77% increase in HR with NE, p=0.12). These results suggest that chronic NIC exposure may cause baseline sympathetic hyperactivity reduced B-AR sensitivity. Findings from this study will have significant implications for youth and young adults who represent the fastest growing group of nicotine users and the cardiac effects of nicotine on this potentially vulnerable population is unknown. Thus, data from this study may have implications for tobacco products and other nicotine containing products.

EFEKTIFITAS MENGUNYAH PERMEN KARET TERHADAP XEROSTOMIA PADA PASIEN CHRONIC KIDNEY DISEASE YANG MENJALANI HEMODIALISA DI RUMAH SAKIT AWAL BROS BATAM TAHUN 2019

Chronic kidney failure or chronic kidney disease is a progressive deviation, kidney function that can not recover, where the body's ability to maintain metabolic balance, fluid and electrolytes, resulting in uremia. This condition is caused by chronic glomerulonephritis, pyelonephritis, uncontrolled hypertension, hereditary lesions, vascular abnormalities, urinary tract obstruction, diabetes, and infections. Today, chronic kidney disease is a disease whose prevalence continues to increase. World Health Organization (WHO) released data on growth in the number of patients with chronic kidney failure in 2013 increased by 50% from the previous year and in America the incidence of chronic kidney failure increased by 50% in 2014 and every year 200,000 Americans undergo hemodialysis Hemodialysis is one way to remove metabolic waste products in the form of a solution and water that is in the blood through a semipermeable membrane or called a dialyzer. The working principle of fluid transfer in hemodialysis is diffusion, osmosis, ultrafiltration and convection. Changes in fluid and electrolyte balance in Chronic Kidney Failure patients result in changes in salivary composition and flow (Fan, Zhang, Luo, Niu &amp; Gu, 2013). In addition to changes in salivary composition and flow, patients with chronic renal failure also experience changes in dry mouth (xerostomia) due to increased ureum concentrations in the blood (Fan et al., 2013). Chewing Gum Xylitol is a candy that no artificial sweeteners activity of chewing gum, low-sugar two eggs approximately 10 minutes to 3x / day for 2 weeks would lead to mechanical stimulation and chemical that can move reflex saliva to stimulate the receptor that is monitored by the trigeminal nerve (V) and facial nerve (VII) as a taste. Sympathetic nerve stimulation will accelerate the secretion of all salivary glands in large quantities which can reduce the sensation of thirst that appears . From the results of research using the method of comparison in get , look the frequency of xerostomia before the intervention mostly dominated by xerostomia weight of 67% and the visible frequency of xerostomia after intervention largely dominated by xerostomia mild 67% , Based on the output "Test Statistics" in table 4.4 above, known p-value is 0,000. Because the value of 0.003 is smaller than &lt;0.05, it can be concluded that "H0 is rejected", or in other words there is "Effectiveness of Chewing Gum Against Xerostomia in Chronic Kidney Disease Patients Who Underwent Hemodialysis at Batam Bros Initial Hospital in 2020

Electrical Stimulation of Afferent Lumbar Sympathetic Nerve Impacts Cardio‐Respiratory Functions in Anesthetized Rats

The lumbar sympathetic chains (LSC) contain post-ganglionic vasodilator and vasoconstrictor fibers that control hindlimb vascular tone. The LSC also contain dorsal root ganglion afferent fibers whose roles in cardiorespiratory status remain poorly understood. The objective of the present study was to characterize the cardiorespiratory responses elicited by electrical stimulation (ES) of a LSC in urethane-anaesthetized male Sprague-Dawley rats (n=6) instrumented to measure/calculate mean arterial blood pressure (MAP), femoral artery blood flow (FBF) and femoral vascular resistance (FVR), brachial artery blood flow (BBF), and brachial vascular resistances (BVR), upper airway pressure (UAP), diaphragmatic EMG, respiratory frequency, inspiratory (iTV) and expiratory (eTV) tidal volumes. The right LSC was identified at the level of L4-L6 and a bipolar electrode was placed for ES (5 Hz, 0.5 msec duration, 0.5 mA amplitude for 10 sec). LSC stimulation caused a distinct pattern of cardiorespiratory responses including (a) a 12% decrease in MAP, (b) 15% decrease in ipsilateral FVR, (c) a 10% decrease in BVR (all measured at the peak decrease in MAP), (d) a 15% increase in iVT, (e) a 10% increase in eVT, (f) a15% increase in respiratory frequency, and (g) a 9% increase in diaphragmatic EMG activity. The result of this study demonstrates that ES of afferent fibers within the LSC elicits an array of cardiorespiratory changes in anesthetized rats that would be consistent with preparing the rats for exercise and for flight.

Fever as a rare combined symptom of degenerative cervical myelopathy: a case report and literature review

A 60-year-old male patient complained of weakness of both legs for one year, intermittent fever for two months, up to 38.0 °C. Physical examination showed bilateral hyperreflexia of knee tendon and positive Hoffman sign on the right side. MR imaging of the cervical spine showed central herniation of the cervical 5-7 disc and compression of the spinal cord. The WBC was normal, C-reactive protein was 24.42mg/l, ESR was 55mm/h, TB antibody, anti acid staining and T-SPOT were negative. Autoantibody was negative and thyroid function was normal. The JOA score was 9 points. During the operation, the herniated disc tissue was taken out for pathological examination and bacterial culture. The posterior longitudinal ligament was removed and no abscess was found. The symptom of asthenia in both legs was relieved and fever disappeared. No growth of aerobe, anaerobe or tubercle bacilli was found in the culture of resected tissue. One year after the operation, the fever did not recur, JOA score increased to 14 points, and MR imaging showed no protrusion in cervical spinal canal. In this case, the fever disappeared after the operation for cervical spondylosis, which may be a special manifestation of sympathetic nerve stimulation or autonomic dysfunction by chronic compression of spinal cord.

Butterfly Pea Flower (Clitoria ternatea Linn.) Extract Ameliorates Cardiovascular Dysfunction and Oxidative Stress in Nitric Oxide-Deficient Hypertensive Rats.

In this study, we examine whether Clitoria ternatea Linn. (CT) can prevent Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced cardiac and vascular dysfunction in rats. Male Sprague Dawley rats were given L-NAME (40 mg/kg, drinking water) and orally administered with CT extract (300 mg/kg/day) or lisinopril (2.5 mg/kg/day) for 5 weeks. The main phytochemical components of the CT extract were found to be flavonoids. The CT extract alleviated the high blood pressure in rats receiving L-NAME. Decreased vasorelaxation responses to acetylcholine and enhanced contractile responses to sympathetic nerve stimulation in aortic rings and mesenteric vascular beds of L-NAME treated rats were ameliorated by CT extract supplementation. Left ventricular hypertrophy and dysfunction were developed in L-NAME rats, which were partially prevented by CT extract treatment. The CT extract alleviated upregulated endothelial nitric oxide synthase expression, decreased plasma nitrate/nitrite levels, and increased oxidative stress in L-NAME rats. It suppressed high levels of serum angiotensin-converting enzyme activity, plasma angiotensin II, and cardiac angiotensin II type 1 receptor, NADPH oxidases 2, nuclear factor-kappa B, and tumor necrosis factor-alpha expression. The CT extract, therefore, partially prevented L-NAME-induced hypertension and cardiovascular alterations in rats. These effects might be related to a reduction in the oxidative stress and renin–angiotensin system activation due to L-NAME in rats.

Restoring Perivascular Adipose Tissue Function in Obesity Using Exercise

PurposePerivascular adipose tissue (PVAT) exerts an anti-contractile effect which is vital in regulating vascular tone. This effect is mediated via sympathetic nervous stimulation of PVAT by a mechanism which involves noradrenaline uptake through organic cation transporter 3 (OCT3) and β3-adrenoceptor-mediated adiponectin release. In obesity, autonomic dysfunction occurs, which may result in a loss of PVAT function and subsequent vascular disease. Accordingly, we have investigated abnormalities in obese PVAT, and the potential for exercise in restoring function.MethodsVascular contractility to electrical field stimulation (EFS) was assessed ex vivo in the presence of pharmacological tools in ±PVAT vessels from obese and exercised obese mice. Immunohistochemistry was used to detect changes in expression of β3-adrenoceptors, OCT3 and tumour necrosis factor-α (TNFα) in PVAT.ResultsHigh fat feeding induced hypertension, hyperglycaemia, and hyperinsulinaemia, which was reversed using exercise, independent of weight loss. Obesity induced a loss of the PVAT anti-contractile effect, which could not be restored via β3-adrenoceptor activation. Moreover, adiponectin no longer exerts vasodilation. Additionally, exercise reversed PVAT dysfunction in obesity by reducing inflammation of PVAT and increasing β3-adrenoceptor and OCT3 expression, which were downregulated in obesity. Furthermore, the vasodilator effects of adiponectin were restored.ConclusionLoss of neutrally mediated PVAT anti-contractile function in obesity will contribute to the development of hypertension and type II diabetes. Exercise training will restore function and treat the vascular complications of obesity.

Suicidal attempt with caffeine overdose treated with dexmedetomidine: a case report

BackgroundCaffeine is a widely used dietary stimulant, and cases of caffeine overdoses, sometimes leading to death, are increasing. We encountered a case of caffeine intoxication resolved with administration of the sedative agent dexmedetomidine.Case presentationWe administered dexmedetomidine for sedation and to suppress sympathetic nerve stimulation in the case of an 18-year-old Japanese male who ingested a massive dose of caffeine with the intention of committing suicide. The patient was in an excited state and had hypertension, sinus tachycardia, and hypokalemia with prominent QT prolongation. After dexmedetomidine administration, the patient’s mental state, hemodynamics, and electrolyte levels were improved immediately. He was discharged without any sequelae 3 days later.ConclusionCases of acute caffeine intoxication with agitation, sympathetic overactivity and adverse cardiac events would benefit with dexmedetomidine treatment.

Changes in Short-Term and Ultra-Short Term Heart Rate, Respiratory Rate, and Time-Domain Heart Rate Variability Parameters during Sympathetic Nervous System Activity Stimulation in Elite Modern Pentathlonists-A Pilot Study.

Monitoring of markers reflecting cardiac autonomic activity before and during stressful situations may be useful for identifying the physiological state of an athlete and may have medical or performance implications. The study aimed to determine group and individual changes in short-term (5 min) and ultra-short-term (1 min) heart rate (HR), respiratory rate (RespRate), and time-domain heart rate variability (HRV) parameters during sympathetic nervous system activity (SNSa) stimulation among professional endurance athletes. Electrocardiographic recordings were performed in stable measurement conditions (Baseline) and during SNSa stimulation via isometric handgrip in 12 elite modern pentathlonists. Significant increases in short-term HR and decreases in time-domain HRV parameters with no changes in RespRate were observed during SNSa stimulation. Significant differences were observed between Baseline (all minutes) and the last (i.e., 5th) minute of SNSa stimulation for ultra-short-term parameters. Analysis of intra-individual changes revealed some heterogeneity in responses. The study provides baseline responses of HR, RespRate, and time-domain HRV parameters to SNSa stimulation among elite pentathlonists, which may be useful for identifying abnormal responses among fatigued or injured (e.g., concussed) athletes. More attention to individual analysis seems to be necessary when assessing physiological responses to sympathetic stimuli in professional endurance athletes.

Neuropeptide Y facilitates P2X1 receptor-dependent vasoconstriction via Y1 receptor activation in small mesenteric arteries during sympathetic neurogenic responses

ATP, norepinephrine and NPY are co-released by sympathetic nerves innervating arteries. ATP elicits vasoconstriction via activation of smooth muscle P2X receptors. The functional interaction between neuropeptide Y (NPY) and P2X receptors in arteries is not known. In this study we investigate the effect of NPY on P2X1-dependent vasoconstriction in mouse mesenteric arteries. Suramin or P2X1 antagonist NF449 abolished α,β-meATP evoked vasoconstrictions. NPY lacked any direct vasoconstrictor effect but facilitated the vasoconstrictive response to α,β-meATP. Mesenteric arteries expressed Y1 and Y4 receptors, but not Y2 or Y5. Y1 receptor inhibition (BIBO3304) reversed NPY facilitation of the α,β-meATP-evoked vasoconstriction. L-type Ca2+ channel antagonism (nifedipine) had no effect on α,β-meATP-evoked vasoconstrictions, but completely reversed NPY facilitation. Electrical field stimulation evoked sympathetic neurogenic vasoconstriction. Neurogenic responses were dependent upon dual α1-adrenergic (prazosin) and P2X1 (NF449) receptor activation. Y1 receptor antagonism partially reduced neurogenic vasoconstriction. Isolation of the P2X1 component by α1-adrenergic blockade allowed faciliatory effects of Y1 receptor activation to be explored. Y1 receptor antagonism reduced the P2X1 receptor component during neurogenic vasoconstriction. α1-adrenergic and P2X1 receptors are post-junctional receptors during sympathetic neurogenic vasoconstriction in mesenteric arteries. In conclusion, we have identified that NPY lacks a direct vasoconstrictor effect in mesenteric arteries but can facilitate vasoconstriction by enhancing the activity of P2X1, following activation by exogenous agonists or during sympathetic nerve stimulation. The mechanism of P2X1 facilitation by NPY involved activation of the NPY Y1 receptor and the L-type Ca2+ channel.

Adrenergic supersensitivity and impaired neural control of cardiac electrophysiology following regional cardiac sympathetic nerve loss

Myocardial infarction (MI) can result in sympathetic nerve loss in the infarct region. However, the contribution of hypo-innervation to electrophysiological remodeling, independent from MI-induced ischemia and fibrosis, has not been comprehensively investigated. We present a novel mouse model of regional cardiac sympathetic hypo-innervation utilizing a targeted-toxin (dopamine beta-hydroxylase antibody conjugated to saporin, DBH-Sap), and measure resulting electrophysiological and Ca2+ handling dynamics. Five days post-surgery, sympathetic nerve density was reduced in the anterior left ventricular epicardium of DBH-Sap hearts compared to control. In Langendorff-perfused hearts, there were no differences in mean action potential duration (APD80) between groups; however, isoproterenol (ISO) significantly shortened APD80 in DBH-Sap but not control hearts, resulting in a significant increase in APD80 dispersion in the DBH-Sap group. ISO also produced spontaneous diastolic Ca2+ elevation in DBH-Sap but not control hearts. In innervated hearts, sympathetic nerve stimulation (SNS) increased heart rate to a lesser degree in DBH-Sap hearts compared to control. Additionally, SNS produced APD80 prolongation in the apex of control but not DBH-Sap hearts. These results suggest that hypo-innervated hearts have regional super-sensitivity to circulating adrenergic stimulation (ISO), while having blunted responses to SNS, providing important insight into the mechanisms of arrhythmogenesis following sympathetic nerve loss.

Sympathetic Input to Multiple Cell Types in Mouse and Human Colon Produces Region-Specific Responses

The colon is innervated by intrinsic and extrinsic neurons that coordinate functions necessary for digestive health. Sympathetic input suppresses colon motility by acting on intrinsic myenteric neurons, but the extent of sympathetic-induced changes on large-scale network activity in myenteric circuits has not been determined. Compounding the complexity of sympathetic function, there is evidence that sympathetic transmitters can regulate activity in non-neuronal cells (such as enteric glia and innate immune cells). We performed anatomical tracing, immunohistochemistry, optogenetic (GCaMP calcium imaging, channelrhodopsin), and colon motility studies in mice and single-cell RNA sequencing in human colon to investigate how sympathetic postganglionic neurons modulate colon function. Individual neurons in each sympathetic prevertebral ganglion innervated the proximal or distal colon, with processes closely opposed to multiple cell types. Calcium imaging in semi-intact mouse colon preparations revealed changes in spontaneous and evoked neural activity, as well as activation of non-neuronal cells, induced by sympathetic nerve stimulation. The overall pattern of response to sympathetic stimulation was unique to the proximal or distal colon. Region-specific changes in cellular activity correlated with motility patterns produced by electrical and optogenetic stimulation of sympathetic pathways. Pharmacology experiments (mouse) and RNA sequencing (human) indicated that appropriate receptors were expressed on different cell types to account for the responses to sympathetic stimulation. Regional differences in expression of α-1 adrenoceptors in human colon emphasize the translational relevance of our mouse findings. Sympathetic neurons differentially regulate activity of neurons and non-neuronal cells in proximal and distal colon to promote distinct changes in motility patterns, likely reflecting the distinct roles played by these 2 regions.

Alkaline Phosphatase Activity Is a Key Determinant of Vascular Responsiveness to Norepinephrine.

Here, we tested the hypothesis that TNAP (tissue nonspecific alkaline phosphatase) modulates vascular responsiveness to norepinephrine. In the isolated, Tyrode's-perfused rat mesentery, 50 µmol/L of L-p-bromotetramisole (L-p-BT; selective TNAP inhibitor, Ki=56 µmol/L) significantly reduced TNAP activity and caused a significant 9.0-fold rightward-shift in the norepinephrine concentration versus vasoconstriction relationship. At 100 µmol/L, L-p-BT further reduced mesenteric TNAP activity and caused an additional significant right-shift of the norepinephrine concentration versus vasoconstriction relationship. A higher concentration (200 µmol/L) of L-p-BT had no further effect on either mesenteric TNAP activity or norepinephrine-induced vasoconstriction. L-p-BT did not alter vascular responses to vasopressin, thus ruling-out nonspecific suppression of vascular reactivity. Since in the rat mesenteric vasculature α1-adrenoceptors mediate norepinephrine-induced vasoconstriction, these finding indicate that TNAP inhibition selectively interferes with α1-adrenoceptor signaling. Additional experiments showed that the effects of TNAP inhibition on norepinephrine-induced vasoconstriction were not mediated by accumulation of pyrophosphate or ATP (TNAP substrates) nor by reduced adenosine levels (TNAP product). TNAP inhibition significantly reduced the Hillslope of the norepinephrine concentration versus vasoconstriction relationship from 1.8±0.2 (consistent with positive cooperativity of α1-adrenoceptor signaling) to 1.0±0.1 (no cooperativity). Selective activation of A1-adenosine receptors, which are known to participate in coincident signaling with α1-adrenoceptors, reversed the suppressive effects of L-p-BT on norepinephrine-induced vasoconstriction. In vivo, L-p-BT administration achieved plasma levels of ≈60 µmol/L and inhibited mesenteric vascular responses to exogenous norepinephrine and sympathetic nerve stimulation. TNAP modulates vascular responses to norepinephrine likely by affecting positive cooperativity of α1-adrenoceptor signaling via a mechanism involving A1 receptor signaling.

Simulated Microgravity Induces Regionally Distinct Neurovascular and Structural Remodeling of Skeletal Muscle and Cutaneous Arteries in the Rat.

Introduction: Mechanical forces and sympathetic influences are key determinants of vascular structure and function. This study tested the hypothesis that hindlimb unloading (HU) exerts diverse effects on forelimb and hindlimb small arteries of rats in functionally different regions of the skeletal muscle and skin. Methods: Male Wistar rats were subjected to HU for 2 weeks, then skeletal muscle arteries (deep brachial and sural) and skin arteries (median and saphenous) were examined in vitro using wire myography or isobaric perfusion and glyoxylic acid staining. Results: HU increased lumen diameter of both forelimb arteries but decreased diameter of the sural artery; the saphenous artery diameter was not affected. Following HU, maximal contractile responses to noradrenaline and serotonin increased in the forelimb but decreased in the hindlimb skeletal muscle feed arteries with no change in skin arteries; all region-specific alterations persisted after endothelium removal. HU increased the sensitivity to vasoconstrictors in the saphenous artery but not in the sural artery. In the saphenous artery, initially high sympathetic innervation density was reduced by HU, sparse innervation in the sural artery was not affected. Electrical stimulation of periarterial sympathetic nerves in isobarically perfused segments of the saphenous artery demonstrated a two-fold decrease of the contractile responses in HU rats compared to that of controls. Conclusion: HU induces contrasting structural and functional adaptations in forelimb and hindlimb skeletal muscle arteries. Additionally, HU had diverse effects in two hindlimb vascular regions. Hyper-sensitivity of the saphenous artery to vasoconstrictors appears to result from the shortage of trophic sympathetic influence. Importantly, HU impaired sympathetically induced arterial vasoconstriction, consistent with the decreased sympathetic constrictor response in humans following space flight.

Feeding brown fat: dietary phytochemicals targeting non-shivering thermogenesis to control body weight

Excessive adipose accumulation, which is the main driver for the development of secondary metabolic complications, has reached epidemic proportions and combined pharmaceutical, educational and nutritional approaches are required to reverse the current rise in global obesity prevalence rates. Brown adipose tissue (BAT) is a unique organ able to dissipate energy and thus a promising target to enhance BMR to counteract a positive energy balance. In addition, active BAT might support body weight maintenance after weight loss to prevent/reduce relapse. Natural products deliver valuable bioactive compounds that have historically helped to alleviate disease symptoms. Interest in recent years has focused on identifying nutritional constituents that are able to induce BAT activity and thereby enhance energy expenditure. This review provides a summary of selected dietary phytochemicals, including isoflavones, catechins, stilbenes, the flavonoids quercetin, luteolin and resveratrol as well as the alkaloids berberine and capsaicin. Most of the discussed phytochemicals act through distinct molecular pathways e.g. sympathetic nerve activation, AMP-kinase signalling, SIRT1 activity or stimulation of oestrogen receptors. Thus, it might be possible to utilise this multitude of pathways to co-activate BAT using a fine-tuned combination of foods or combined nutritional supplements.

Selective Peripheral Chemoreceptor Hyperreflexia Evoked after Sympathetic Stimulation

Previous studies have demonstrated that the integrity of the carotid bodies is essential for the development and maintenance of hypertension. In this condition, both increased tonicity and hyperreflexia are displayed by chemosensitive neurons in the petrosal ganglia of spontaneous hypertensive rats (SHR). However, what drives carotid body hyper‐excitability is not known. We hypothesised this was triggered by the sympathetic nerves innervating the carotid body, which originate from the superior cervical ganglion (SCG). The aim of our study was test if activation of the SCG could modulate carotid body activity. Experiments were carried out in 6 juvenile Wistar rats (60–80g) using the decerebrated in situ working heart‐brainstem preparation (WHBP). Simultaneous recordings of phrenic (PN) and thoracic sympathetic nerves (tSNA) were obtained using glass suction electrodes. Heart rate (HR) was derived from the electrocardiogram (ECG). Chemoreflex was activated using NaCN (50μL, 0.04%, i.a.) and the SCG was stimulated electrically (ES; 30Hz, 2 ms, 10V) using a Grass SD9 stimulator via a bipolar microelectrode. The chemoreflex was evoked before and immediately after ES of the SCG. Changes in sympathetic activity, perfusion pressure, phrenic and heart rate were analysed quantitatively. Data are displayed as mean ± SEM with a level of significance set at P&lt;0.05; differences were tested using paired student‐t test.The only component of the chemoreflex augmented by SCG stimulation was the evoked increase in sympathetic activity. In Wistars, the control response of 29.3 ± 3.2% from baseline was augmented to 46.04 ± 3.58% after ES (P=0.006). Within 10 min of the stimulation, the sympatho hyperreflexia had returned to control (20.24 ± 5.96%). SHR also presented sympatho hyperreflexia (43.0 ± 6.3 vs 62.9 ± 9.2 %, P= 0.015) but the change of sensitization was of similar magnitude between rat strains. The SCG induced carotid body hyperreflexia was prevented by application of lignocaine into the SCG. We conclude that stimulation of the efferent sympathetic nerves innervating the carotid body can increase the gain of the chemoreflex symathoexcitatory response. We are currently assessing whether chemoreflex hyperreflexia observed in neurogenic hypertension is mediated by sympathetic nerves innervating the carotid body.Support or Funding InformationHealth Research Council of New Zealand

Long‐Term Intake of Capsiate Increases Fat Accumulation according to Reduced‐Energy Expenditure, which Is Occurred by Increased‐Immobility in Diet‐Induced Obese Mice but not in Trained.

PurposeHaving a similar weight‐loss effect which is occurred by the sympathetic nervous stimulation of capsaicin, capsiate (CAP) began to spotlight because of its much less pungency than capsaicin’s. However, previous studies have tended to focus on short‐term (to 2 from 4 weeks) effect of CAP with normal diet. Therefore, the purpose of this study was to identify the effects of long‐term CAP intake and high‐fat diet (HFD) on energy expenditure and fat accumulation. And we also investigated whether there was a synergistic effect on fat accumulation when exercised together.MethodsThe male 8‐week‐old ICR mice were divided into 4 groups. Sed0 (sedentary; non‐trained), Sed10 (sedentary and 10 mg/kg of CAP), Tr0 (moderate intensity‐trained) and Tr10 (moderate intensity‐trained and 10 mg/kg of CAP). All mice freely accessed to water and HFD.Treadmill training was conducted with 5times a week for 8 weeks. The exercise intensity was increased from 20 min at 13 m/min to 60 min at 16 m/min while maintaining the 8° slope. The Tr groups were administrated each supplement 30 minutes before training. Tail‐suspension test was performed by suspending a mouse from horizontal bar. Mouse was suspended by its tail for 6min, and the immobility time was measured during the last 5min, with the first minute ignored to allow for habituation.ResultsLong‐term intake of CAP did not significantly change the body weight gain in the both sedentary and trained group. However, the total food intake was significantly lower in the Sed10 than in the Sed0 and reversely greater in the Tr10 than in the Tr0. Interestingly, the total abdominal fat was significantly higher in the Sed10 than in the Sed0 and the training showed a tendency to reverse this result but there was no significant difference within the Tr group. From the resting metabolic rate results, the total energy expenditure was slightly lower in the Sed10 than in the Sed0 but there was no significant difference within both Sed and Tr group. However, there was significant difference between the Sed10 and the Tr10 but not between the Sed0 and the Tr0. From the tail suspension test results, the immobility time was significantly longer in the Sed10 than in the Sed0 and there was no significant difference within the trained group. But the BDNF protein level in the hippocampus was no different.ConclusionIn summary, these results show that long‐term intake of CAP with HFD increased fat accumulation according to reduced‐energy expenditure, which seemed to be occurred by immobility. But the moderate intensity‐exercise reversed these results. Therefore, if CAP is used to increase energy expenditure over long periods of time, we suggest that exercise and/or dietary control should be properly combined. Furthermore, these findings provide a slight insight that long‐term intake of CAP with HFD could be assessed by the neuropathological approach.

Obesity Increases Microvascular Contractility in Response to Sympathetic Nerve Stimulation

Obesity impairs vasodilation and increases contractility in small mesenteric resistance arterioles. The mesenteric microvasculature is innervated by sympathetic and sensory perivascular nerves; however, it isn’t known if changes in innervation contribute to microvascular dysfunction in obesity. The current aim was to characterize the sympathetic and sensory nerve‐mediated responses of isolated mesenteric arterioles from lean and obese mice. We placed 6‐week‐old mice (C57BL/6) on either low or high‐fat diets for 12 weeks. We then isolated third order mesenteric arterioles and used pressure myography to record the effect of perivascular nerve activation by electrical field stimulation (EFS). EFS (20 V, 3 Hz, 2 ms pulse width) caused vasoconstriction which was attenuated by the voltage‐gated Na+ channel blocker tetrodotoxin (TTX, 1 μM). Vasoconstriction (% maximal constriction) was larger in vessels from obese (50% ± 2) mice compared to those from lean (22 ± 5%) animals (P&lt;0.001, n=3, t‐test). To assess the effect of obesity on sensory innervation, vessels were treated with guanethidine 10 μM to suppress sympathetic nerves, and precontracted with 1 μM phenylephrine. Under these conditions, EFS evoked similar relaxations (% maximal relaxation in zero calcium and sodium nitroprusside) in the lean (36% ± 11) and obese (45% ± 16) groups (P&gt;0.5, n=3, t‐test). In conclusion, these data show that during obesity the contractile response to sympathetic innervation is increased without change in the dilatory response to sensory innervation.Support or Funding InformationThis work was supported by NIH grant HL142906.

Comparison of Neurotransmitter Release from Perivascular Nerves in C57BL/6J Mice and Wistar Rats

It is thought that sympathetic nerve activation stimulates arterial constriction predominately through the release of three neurotransmitters: norepinephrine (NE), adenosine triphosphate (ATP) and neuropeptide Y (NPY). The aim of the current study was to examine the composition of neurotransmitter released in response to sympathetic nerve stimulation in mesenteric arteries of two commonly used wild‐type animal models. Isolated mesenteric arteries from male C57BL/6J mice and Wistar rats were mounted in a Danish Myotechnology 2‐Channel Wire Myograph System and isometric force measurements were recorded. Electrical field stimulation (EFS) was used to stimulate sympathetic perivascular nerves (PVNs) to release neurotransmitters in the presence and absence of the adrenergic receptor blocker phentolamine and/or purinergic receptor blocker NF449. Phentolamine alone blocked a significant proportion of the contractile response evoked by EFS in both mice and rats, suggesting that NE is the main sympathetic neurotransmitter in both species. Treatment with NF449 alone blocked a small proportion of the contractile response evoked by EFS in mice but did not have a significant effect in rat, suggesting that ATP may play a more important role in mice. The application of both phentolamine and NF449 nearly completely blocked the contractile response to EFS in mouse mesenteric arteries; however, in rat, a proportion of the contractile response, roughly equivalent to the response obtained in the presence of phentolamine alone, was still observed. These data suggest that the neurotransmitter composition is different between mice and rats, in particular mouse mesenteric sympathetic PVNs release NE and ATP while rat mesenteric sympathetic PVNs release NE and another non‐purinergic neurotransmitter(s).

Fast in vivo detection of myocardial norepinephrine levels in the beating porcine heart.

The sympathetic nervous system modulates cardiac function by controlling key parameters such as chronotropy and inotropy. Sympathetic control of ventricular function occurs through extrinsic innervation arising from the stellate ganglia and thoracic sympathetic chain. In the healthy heart, sympathetic release of norepinephrine (NE) results in positive modulation of chronotropy, inotropy, and dromotropy, significantly increasing cardiac output. However, in the setting of myocardial infarction or injury, sympathetic activation persists, contributing to heart failure and increasing the risk of arrhythmias, including sudden cardiac death. Methodologies for detection of norepinephrine in cardiac tissue are limited. Present techniques rely on microdialysis for analysis by high-performance liquid chromatography coupled to electrochemical detection (HPLC-ED), radioimmunoassay, or other immunoassays, such as enzyme-linked immunosorbent assay (ELISA). Although significant information about the release and action of norepinephrine has been obtained with these methodologies, they are limited in temporal resolution, require large sample volumes, and provide results with a significant delay after sample collection (hours to weeks). In this study, we report a novel approach for measurement of interstitial cardiac norepinephrine, using minimally invasive, electrode-based, fast-scanning cyclic voltammetry (FSCV) applied in a beating porcine heart. The first multispatial and high temporal resolution, multichannel measurements of NE release in vivo are provided. Our data demonstrate rapid changes in interstitial NE profiles with regional differences in response to coronary ischemia, sympathetic nerve stimulation, and alterations in preload/afterload.NEW & NOTEWORTHY Pharmacological, electrical, or surgical regulation of sympathetic neuronal control can be used to modulate cardiac function and treat arrhythmias. However, present methods for monitoring sympathetic release of norepinephrine in the heart are limited in spatial and temporal resolution. Here, we provide for the first time a methodology and demonstration of practice and rapid measures of individualized regional autonomic neurotransmitter levels in a beating heart. We show dynamic, spatially resolved release profiles under normal and pathological conditions.