bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemosensitive Cardiac Afferent Reflexes in Mice: Are they Altered in Hypertrophic Cardiomyopathy?
Authors: Larson Robert A. , Chapleau Mark W. 
Published: June 2021

Hypertrophic cardiomyopathy (HCM) is a life‐threatening disease caused by sarcomere gene mutations. Hallmark features include myocyte disarray, left ventricular hypertrophy, fibrosis, and increased risk of arrhythmias and sudden death. Cardiac norepinephrine spillover is augmented in humans with HCM. Similarly, our group has previously reported that cardiac sympathetic tone is increased and vasomotor sympathetic tone is decreased in transgenic mice with cardiac‐specific expression of mutated alpha‐tropomyosin (Glu180Gly), a model of human HCM. Specific aims of this study were to develop protocols to evaluate cardiac reflexes evoked by activation of vagal and ‘sympathetic’ afferents in anesthetized mice, and test the hypothesis that alpha‐tropomyosin mutant HCM mice exhibit enhanced heart rate responses to activation of cardiac ‘sympathetic’ afferents. Cardiac reflexes were evoked via injection of the TRPV1 receptor agonist capsaicin (25 & 50 ng/g, IV) in mice anesthetized with ketamine (91μg/g) and xylazine (9.1 μg/g). Injection of capsaicin (50 ng/g, IV) in C57BL6 mice evoked rapid decreases in heart rate (HR) (−131±17bpm) and mean arterial pressure (MAP) (−30.1±2.7 mmHg) followed by delayed increases in HR (+12.5±7.6bpm) and MAP (+12.7±3.7 mmHg) (n=6, p<0.05). Responses were dose‐dependent and repeatable. Bilateral cervical vagotomy abolished the bradycardic/depressor responses to capsaicin and enhanced the delayed increases in HR (+22.6±4.1bpm) and MAP (+27.6±1.7 mmHg) (n=5). All responses to capsaicin were essentially abolished after ganglionic blockade (p<0.05, n=3) confirming the responses were neurally mediated. The tachycardic response to capsaicin (25ng/g, IV) after vagotomy was significantly (p<0.05) augmented in HCM mice (+32±11bpm, n=5) compared with their wild‐type (WT) controls (+11±3bpm, n=6). In contrast, the MAP response to capsaicin was similar between HCM (+8.5±2.5 mmHg, n=5) and WT (+6.3±1.6 mmHg, n=6). We conclude: (1) Measurements of reflex responses to capsaicin before and after vagotomy enable assessment of both inhibitory and excitatory reflexes in mice, and (2) HCM mice demonstrate an exaggerated tachycardic response to injection of capsaicin, presumably reflecting an increased sensitivity of cardiac ‘sympathetic’ afferent nerves.Support or Funding InformationNIH T32HL007121, AAS‐Lundbeck Fellowship, NIH HL14388, VA 1BX001414This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Mechanisms of Cross‐Talk between Leptin and Angiotensin within the Arcuate Nucleus for the Control of Metabolic Rate
Authors: Sapouckey Sarah A. , Deng Guorui , Gibson‐Corley Katherine N. , Cui Huxing , Sebag Julien A. , Grobe Justin L. 
Published: June 2021

Recent studies from our laboratory have demonstrated that within the arcuate nucleus of the hypothalamus (ARC), angiotensin II (ANG) type 1A receptors (AT1A) are expressed by the subset of neurons which express both the leptin receptor (LepR) and agouti‐related peptide (AgRP). AT1A expression in this subpopulation of AgRP neurons is critically involved in the integrative control of thermogenic adipose sympathetic nerve activity (SNA) and thereby resting metabolic rate (RMR) by various stimuli including leptin. It remains unclear, however, how LepR signaling results in AT1A activation within AgRP neurons. We hypothesize that activation of LepR (i) increases de novo synthesis of AGT and thus autocrine and/or paracrine ANG signaling within the ARC, and (ii) increases AT1A expression and trafficking to the cell membrane, increasing AgRP neuron sensitivity to ANG. Consistent with our first hypothesis, AGT is co‐localized within the ARC of C57BL/6J mice with cells expressing AgRP and LepR, as determined by fluorescent in situ hybridization and confocal microscopy. Studies of an immortalized mouse hypothalamic cell line (N43/5 cells, which exhibit a gene signature typical of AgRP cells) demonstrate that AGT mRNA is increased in response to leptin treatment. Selective genetic disruption of the AGT gene in LepR or AgRP neurons (AGTLepR‐KO and AGTAgRP‐KO mice) has no effect on energy flux under baseline chow‐fed conditions, though ongoing studies are focused on examining metabolic responses of these animals to high fat diet and leptin. Consistent with our second hypothesis, leptin application to N43/5 cells results in increased AT1A mRNA, and leptin injection in wildtype C57BL/6J mice increases AT1A mRNA in the ARC. Ongoing studies utilizing the new HiBiT‐tagging system (Promega) support cell surface localization of AT1A in the N43/5 cell line, which is increased by leptin treatment and reduced by ANG application. Ongoing studies are aimed at (i) examining the roles of pSTAT3, PI3K and ERK in the stimulation of AGT and AT1A expression by leptin, (ii) further characterizing AGTLepR‐KO and AGTAgRP‐KO mice by examining SNA and RMR in response to high fat diet and leptin, and (iii) using the HiBiT extracellular detection system to clarify the mechanism(s) by which leptin modulates cell surface localization of AT1A.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Spontaneous Baroreflex Control of Muscle Sympathetic Nerve Activity in Humans: Standardizing Analysis Procedures
Authors: Holwerda Seth W. , Carter Jason R. , Yang Huan , Pierce Gary L. , Fadel Paul J. 
Published: June 2021

Beat‐to‐beat variations in muscle sympathetic nerve activity (MSNA) are strongly related to diastolic blood pressure (DBP) fluctuations, and the use of spontaneous occurring bursts of MSNA at rest to determine sympathetic baroreflex sensitivity has become more prevalent. However, published results using spontaneous sympathetic baroreflex sensitivity have lacked standard methodology for analysis. Indeed, there have been variations in the duration of the recording used, the size of the DBP bins (1‐, 2‐, 3‐mmHg), and strength of the linear regression r‐values accepted. Thus, we sought to comprehensively examine the influence of these varying analysis procedures on spontaneous sympathetic baroreflex sensitivity. Our goal was to provide a standardized procedure that would allow for consistent and comparable results across laboratories. In a collective group of subjects (n=150), weighted linear regression analysis between MSNA and DBP was performed with MSNA expressed as either burst incidence (bursts/100heartbeats) or total MSNA (summation of MSNA burst amplitude relative to number of cardiac cycles). Resting MSNA was analyzed over a 10‐min baseline period, and subsequently segregated into separate 5‐, 2‐, and 1‐min segments to examine the influence of baseline duration on the weighted linear regression. MSNA was averaged over 1‐, 2‐, or 3‐mmHg DBP ranges (bins) to examine the influence of bin size. Also, in a subset of subjects (n=35), the modified Oxford technique (intravenous infusion of sodium nitroprusside followed by phenylephrine) was performed for comparison. The average slope of the linear regressions for resting MSNA burst incidence and total MSNA progressively increased as the baseline duration decreased with 1‐min duration being significantly greater than 10 min (P<0.05); however, correlation coefficients were reduced with the shorter durations. Indeed, the 10‐min baseline durations most frequently yielded statistically significant probability values for linear regressions (P<0.05), which closely reflected the p‐values obtained during the modified Oxford. Interestingly, although bin size (1‐, 2‐, 3‐mmHg) had no major influence on the average slope of the regressions (P>0.05), correlation coefficients progressively increased with bin size such that the highest correlation coefficients were observed for the 3‐mmHg bin size for each time duration segment. Overall, the 10‐min durations and 3‐mmHg bin size yielded the highest correlation coefficients. Collectively, these findings suggest that the duration of the recording used for analysis impacts the statistical validity of the r‐values defining the slopes for spontaneous sympathetic baroreflex sensitivity, whereas larger bin size improves the r‐value but has less influence on the p‐value.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Augmentation of M‐Current and Increased Synaptic Efficacy at Intrinsic Cardiac Neurons Contributes to an Enhanced Cardiac Responsiveness to Vagal Nerve Stimulation in the Infarcted Porcine Heart
Authors: Tompkins John D. , Buckley Una , Salavatian Siamak , Shivkumar Kalyanam , Ardell Jeffrey 
Published: June 2021

Imbalances to autonomic regulation of cardiac function contribute to risk for arrhythmia after myocardial infarction (MI). We tested the hearts responsiveness to vagal nerve stimulation (VNS), 8 wks after MI, to determine if parasympathetic control of the heart is altered in MI pigs. A significantly greater bradycardic response was elicited in MI animals during 20Hz stimulation. Intracellular voltage recordings from whole‐mount preparations of intrinsic cardiac neurons (ICNs) were subsequently used to assess whether alterations in neuronal membrane properties or synaptic transmission underlie the observed increase in responsiveness to VNS in MI animals. General membrane properties (resting membrane potential, input resistance, action potential amplitude/duration, afterhyperpolarization amplitude/duration) of ICNs from control and MI pigs were not different, but ICN excitability was significantly depressed in MI pigs. Testing synaptic efficacy revealed a greater proportion of strong (high AP probability) vs weak synapses (low AP probability) in MI animals. Tetanic stimulation (20Hz) of interganglionic nerve bundles elicited slow excitatory postsynaptic potentials (sEPSPs) in a significantly greater subset of MI ICNs (10/22) vs controls (4/26). The sEPSP persisted in hexamethonium (500uM) but was blocked by atropine (1uM), indicating mediation by cholinergic inhibition of M‐current. Application of 1mM Ba2+ increased excitability of ICNs from both control and MI animals further supporting a role for M‐current in the regulation of porcine ICN excitability. In hexamethonium, the amplitude of the sEPSP was significantly greater in MI ICNs. In conclusion, we identify a important role of M‐current in the regulation of the excitability of porcine ICNs, and demonstrate enhanced membrane depolarization of ICNs from MI animals after presynaptic stimulation due, in part, to greater inhibition of IM during tetanic nerve stimulation which may underlie the enhanced sensitivity to VNS in MI pigs.Support or Funding InformationThis work was supported in part by NIH grant OT2OD023848.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Copeptin Responses to Isotonic and Hypertonic Saline Infusion in Healthy Adults
Authors: Suh Hyun‐Gyu , Jansen Lisa T. , Sprong Cameron , Adams J.D. , Butts Cory L. , Seal Adam D. , Scott Dylan , Melander Olle , Lemetais Guillaume , Dolci Alberto , Vanhaecke Tiphaine , Perrier Erica T. , Kirkland Tracie , Kavouras Stavros A. 
Published: June 2021

Copeptin, a c‐terminal segment of arginine vasopressin (AVP) prohormone, has equimolar secretion to AVP in response to osmotic, stress‐related, and hemodynamic stimulation. For this reason, and because of the difficulties in measuring AVP directly linked to its short half‐life, copeptin has been used as a stable and sensitive surrogate marker for AVP for various clinical indications. However, the plasma copeptin response to osmotic stimulation remains poorly documented.PURPOSEExamine the plasma copeptin response to plasma hyperosmolality induced by hypertonic saline infusion.METHODSSixty healthy adults (50% male, age: 30±1 y, weight: 78.2±15.2 kg, body mass index: 26.9±4.0 kg·m−2) were infused intravenously with 3% (HYPER) or 0.9% (ISO) NaCl for 2 h (0.1 ml·kg−1·min−1) in a counterbalanced, cross‐over design. Blood samples were collected every 30 minutes. Plasma osmolality (POsm), copeptin (PCop; BRAHAMS copeptin proAVP, Thermo Fisher Scientific, Germany), and sodium (PNa) were measured, and changes in plasma volume (PV) were calculated from hematocrit and hemoglobin using the Dill & Costill equation.RESULTSFollowing the HYPER trial, PNa increased from 136±2 mmol ·L−1 to 146.5±3 mmol ·l−1 (P < 0.001), with PV expansion of 18.7±7.3% (P < 0.001). Both POsm and PCop increased significantly (0 min: 286±3 mmol·kg−1 and 4.5±3.7 pmol·L−1; 120 min: 305±4 mmol·kg−1 and 20.4±12.8 pmol·L−1, respectively, P < 0.001). Mean (95% CI) PCop increased with increasing POsm: 3.2 (2.5–3.8) pmol·L−1 for POsm ≤ 284.9 mmol·kg−1; 5.4 (3.8–7.0) pmol·L−1 for POsm 285–289.9; 6.2 (4.3–8.0) pmol·L−1 for POsm 290–294.9; 8.5 (7.1–9.9) pmol·L−1 for POsm 295–299.9; 12.3 (10.2–14.4) pmol·L−1 for POsm 300–304.9; and 19.2 (16.3–22.2) pmol·L−1 for POsm ≥ 305 mmol·kg−1. In contrast, during the ISO trial PNa remained unchanged during the 2‐h infusion (135.9±1.9 vs. 137.6±1.6 mmol·L−1), while PV expanded by 10.5±4.4% (P < 0.001 compared to baseline; P < 0.001 compared to HYPER). Neither POsm (0 min: 285±4,120 min: 287±3 mmol·kg−1) nor PCop (0 min: 4.1±1.8, 120 min: 3.8±3.0 pmol·L−1) were affected during the ISO trial.CONCLUSIONPlasma copeptin was stimulated by increased plasma osmolality during a hypertonic infusion.Support or Funding InformationThis research was supported by Danone ResearchThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Synaptic Plasticity in the Dorsal Vagal Complex: Role in Salt Intake and Alteration by Estrogen
Authors: Toal Sheri L. , Curtis Kathleen S. 
Published: June 2021

Sodium depletion produced by the natriuretic‐diuretic, furosemide (Furo) stimulates salt intake that increases progressively with repeated Furo treatments. Hormonal, osmotic, and neural signals regarding perturbations in sodium balance are initially processed within neurons and glia of the hindbrain dorsal vagal complex (DVC). Thus, plastic changes to glia and synaptic proteins can alter the effectiveness of synapses in the dorsal vagal complex to propagate signals to forebrain areas involved in body fluid regulation and thereby produce progressive increases in salt intake. Central actions of estrogen contribute to sex differences in a variety of adaptive behaviors, including salt intake in response to Furo treatment. Therefore, our objective was to assess the effect of estrogen on the expression of glial fibrillary acidic protein (GFAP; a marker for glia) and synaptotagmin 4 and calcium calmodulin kinase II (SYT4 CaMKII; synaptic proteins) in the DVC in response to repeated treatments with Furo. Adult female rats were ovariectomized, allowed to recover for 7 days, and then given estradiol benzoate (EB; 10 μg/0.1 ml oil, sc) or oil vehicle (OIL; 0.1 ml, sc) each week for 3 weeks. Rats were injected weekly with Furosemide (5 mg/kg, sc) or 0.15 M NaCl 18–24 hours after injection on week 1 and 2; and rats were also given 3‐hr access to one bottle of deionized water and one bottle of 0.5 M NaCl (salt) without food. On week 3, rats were terminated via decapitation 18–24 hours after the second injection, and the brains were flash frozen in liquid nitrogen, homogenized, and stored at −80°C. Frozen tissue punches from DVC were immunoblotted for GFAP (Millipore MAB360 mouse anti‐GFAP; 1:6000), CaMKII (Thermo Fisher MA1‐048 mouse anti‐CaMKII; 1:2000), synaptotagmin 4 (Thermo Fisher PA5‐52709 rabbit anti‐SYT4; 1:250), and β‐actin (#4970; Cell Signaling rabbit anti‐ β‐actin; 1:1000). Salt intake was increased in furosemide treated rats compared to isosaline treated rats independent of number of depletions. Estradiol produced a greater increase in salt intake compared to oil‐treated rats after first furosemide‐induced sodium depletion. Water intake was increased in furosemide treated rats compared to isosaline treated rats. Repeated furosemide treatment altered the expression of GFAP, SYT4, and CaMKII in the DVC. Preliminary analysis suggests estradiol may alter expression of GFAP, SYT4, and CaMKII in the DVC.Support or Funding InformationSupported by OCAST HR12‐196This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Hypoxia Avoidance Behavior in two Air‐breathing Fishes
Authors: Jew Corey , Hicks James W. 
Published: June 2021

Aquatic animals are known to be sensitive to low oxygen environments. Aquatic hypoxia can limit an animal's capacity for aerobic metabolism, reducing its ability for locomotion, growth, reproduction, and survival. It is thus important for a fish to be able to detect and avoid hypoxic environments or develop an auxiliary method for obtaining oxygen, such as breathing air. Air breathing allows a fish to access environments and maintain aerobic metabolism independent of environmental oxygen levels. In this study, we test two air‐breathing fishes, Polypterus and Pangasianodon, for the presence of a hypoxia avoidance behavior both when allowed to freely breathe air and when air access is denied. Fish were placed in a shuttle box consisting of two circular arena attached to allow free movement between the two. A fish was placed in the shuttle box and monitored as oxygen was reduced on one arena and then returned to normal while the other side was reduced. Separate trials were run with a subsurface net to deny air breathing. Polypterus did not show a hypoxia avoidance behavior when allowed air access, however it did when denied air access, similar to a solely water‐breathing fish. Pangasianodon did not show a hypoxia avoidance behavior with or without air access even at oxygen levels below its air‐breathing threshold and Pcrit. Pangasianodon has been shown to survive beyond 25 h below its Pcrit without air access, suggesting that this animal maintains physiological mechanisms for hypoxia tolerance (e.g., metabolic suppression) not present in other air‐breathing fishes, such as Polypterus. Further studies will compare the ability of Polypterus and Pangasianodon to reduce metabolism in response aquatic hypoxia.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Intermittent Fasting Suppresses Activity‐Associated Energy Expenditure and Enhances Weight Loss in Obesity‐Prone Rats
Authors: Titus Amber R. , Davis Ashley E. , Britton Steven L. , Koch Lauren G. , Novak Colleen M. 
Published: June 2021

Weight and fat loss occur when total energy expenditure (EE) is higher than energy input. This can be achieved by lowering caloric input through altering diet, or by increasing total EE. Activity‐associated EE is suppressed during weight loss and maintenance of reduced weight; this occurs through decreased physical activity levels along with increased fuel economy of activity. These adaptations take time to occur. Both activity‐associated EE and resting EE have been shown to decrease during calorie restriction‐induced weight loss in rats. Recently, attention is being paid to alternatives to calorie‐restriction, such as time‐restricted feeding approaches including intermittent, or alternate‐day, fasting. We have found that, unlike daily calorie‐restriction, intermittent fasting achieves a superior result in obesity‐prone rats compared to their lean counterparts. Here, we investigate the potential contribution of physical activity‐associated EE to the altered energy balance contributing to weight loss during intermittent fasting. We examined female high‐and‐low‐capacity runners (HCR and LCR, respectively), rats artificially selected for high and low intrinsic aerobic capacity. HCR are lean and more physically active than their obesity‐prone LCR counterparts. We induced equivalent weight loss within phenotype using intermittent fasting and daily calorie‐restriction, and measured activity‐associated EE during treadmill walking. Calorie‐restriction and intermittent fasting induced equivalent suppression of activity‐associated EE in both HCR and LCR. As we saw previously, intermittent fasting was significantly more effective in inducing weight loss in the obesity‐prone LCR than in HCR. Interestingly, our data do not support the hypothesis that the enhanced weight loss occurs through a release from adaptive thermogenesis in activity‐associated EE. There was also no difference in activity‐associated EE between fed and fasted days in the intermittent‐fasted rats. This implicates intermittent fasting as a superior means of weight loss in obesity‐prone rats, and suggests that the efficacy of intermittent fasting might also vary between people.Support or Funding InformationFunding: NIH NIDDK R15‐DK‐097644 and R15‐DK‐108668 to Colleen M Novak; P40 OD021331 to Lauren G Koch. Resource for Rat Genetic Models of Aerobic Capacity: P40 OD021331(Lauren G Koch, Principal Investigator; Steven L Britton, Co‐Investigator)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.