bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impaired Baroreflex Function during Rest and Graded Orthostasis in Women with PTSD
Authors: Yoo Jeung‐Ki , Badrov Mark B , Parker Rosemary S , Anderson Elizabeth H , Dorn Raymond Peter , Suris Alina M , Levine Benjamin D , Fu Qi 
Published: June 2021

Post‐traumatic stress disorder (PTSD) is more prevalent in women and associated with significantly higher risk of hypertension and cardiovascular disease. The underlying mechanisms are unclear, but impaired baroreflex function and vasomotor sympathetic neural control may be involved. We hypothesized that women with PTSD would have an impaired baroreflex control of muscle sympathetic nerve activity (MSNA). MSNA and hemodynamics were measured supine and during 30º and 60º head‐up tilt (HUT) in 14 women with PTSD and 14 healthy women (Controls). Sympathetic baroreflex sensitivity(BRS) was quantified using the slope of the linear correlation between MSNA and diastolic pressure during spontaneous breathing. Age and body mass index were not different between groups. Supine resting MSNA was greater in women with PTSD (PTSD vs. Controls: 27±3 vs. 14±3 bursts/min; P=0.002, mean±SEM). Sympathetic BRS was impaired in women with PTSD compared to controls in the supine position (PTSD vs. Controls: −43±7 vs. −64±9 units 100beats−1 mmHg−1, P=0.02). It remained lower in women with PTSD during 30º and 60º HUT (posturexgroup interaction P=0.1, time P=0.003, group P=0.03). MSNA response to the graded HUT was not different between groups but the efficacy of MSNA for vasoconstriction was greater in women with PTSD (HUT 30: 1.8±0.5 vs.0.9±0.4 %TPR/%totalMSNA; P=0.01, HUT60: 1.2±0.4 vs. 0.7±0.3; P=0.04). Our findings demonstrate that women with PTSD have decreased sympathetic BRS and it may contribute to augmented sympathetic activity. The higher efficacy of MSNA for vasoconstriction in PTSD suggests greater sympathetic vascular transduction and/or other nonadrenergic mechanisms responsible for vasoconstriction. These results may explain, in part, the underlying mechanisms for the greater risk of developing hypertension and cardiovascular disease in women with PTSD.Support or Funding InformationSupported by the Harry S. Moss Heart TrustThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Alpha Intrusion during Rapid Eye Movement (REM) Sleep Increases Blood Pressure
Authors: Greenlund Ian M , Cunningham Hannah A , Tikkanen Anne L , Durocher John J , Smoot Carl A , Carter Jason R 
Published: June 2021

Rapid eye movement (REM) sleep is characterized by low voltage, mixed frequency electroencephalography (EEG). A hallmark of REM sleep includes episodic increases of blood pressure and heart rate, and a higher incidence of adverse cardiovascular events such as myocardial infarction and stroke. In pathological conditions such as fibromyalgia and other chronic pain conditions, alpha frequencies (8–13 Hz) are often observed during normal EEG frequencies, a phenomena referred to as alpha intrusion. The impact of alpha intrusion on blood pressure during REM sleep remains unknown. The purpose of this study was to utilize finger plethysmography to determine the impact of alpha intrusion on beat‐to‐beat blood pressure and heart rate during REM sleep. Eleven participants (6 female, 22±1 years, 28±1 kg/m2) were equipped with overnight finger plethysmography (NOVA, Finapres) and standard 10–20 EEG electrode placement for quantification of sleep stage (SleepWorks, Natus). Overnight EEG was scored according to the American Academy of Sleep Medicine (AASM) guidelines by a trained sleep technician and board‐certified sleep physician. EEG signals were filtered with a common low pass (35 Hz), high pass (0.5 Hz), and notch (60 Hz) filter. Occipital EEG was analyzed using an original MATLAB® code, applying a short‐term Fourier transform function (i.e., spectral analysis) with sliding window parameters of 10 seconds by 5 seconds. Alpha frequencies were normalized to the entire overnight EEG to quantify alpha power density. During the final REM episode, a representative 30 second sample of maximum alpha intrusion was selected, and compared to 30 second baseline and recovery periods immediately preceding and following the maximum alpha intrusion. Each EEG sample was free of any scorable arousals, apneic events, or significant limb movements. Continuous recordings of systolic arterial pressure (SAP), diastolic arterial pressure (DAP), and heart rate (HR) were analyzed during these timeframes. Statistical analysis included repeated measures ANOVA (p<0.05). Alpha power density increased during alpha intrusion (0.228 ± 0.02 μV to 0.347 ± 0.04 μV; p<0.001), and returned to baseline levels during recovery (0.205±0.03 μV). Similarly, SAP increased during alpha intrusion (121 ± 5 mmHg to 124 ± 5 mmHg; p=0.038), and returned to baseline during recovery (121 ± 6 mmHg). DAP tended to increase during alpha intrusion (p = 0.08), while HR did not change with alpha intrusion. These results suggest alpha intrusion increases REM blood pressure. These findings have potential clinical relevance given the higher incidence of adverse cardiovascular events during early morning REM sleep.Support or Funding InformationSupport provided by the National Institutes of Health (AA‐024892) and the Portage Health Foundation.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Reduced Baroreflex Function in the STZ‐Induced Rat Model of Alzheimer's Disease
Authors: Ehlen John Christian , Ostrowski Daniela , Ostrowski Tim Daniel 
Published: June 2021

BackgroundAlzheimer's disease (AD) is a progressive neurodegenerative disorder causing multiple autonomic conditions including cardiovascular impairments. The inability to maintain blood pressure via baroreflex regulation is up to 5.6 times more prevalent in AD and patients present most commonly with orthostatic hypotension. This study aimed to assess the influence of AD on autonomic regulation of blood pressure using the streptozotocin (STZ)‐induced AD rat model, which mimics many hallmark symptoms of sporadic AD in humans.MethodsMale Sprague‐Dawley rats (345 ± 18 g) were randomly divided into two groups and subjected to intracerebroventricular injection of either vehicle (citrate buffer, CTL) or 2 mg/kg STZ in citrate buffer. After two weeks, memory performance (Morris water maze, MWM), baroreflex function (via femoral cannulation), and heart rate variability (HRV) were evaluated.ResultsMWM verified memory impairment in STZ‐treated rats when compared to CTL (p≤0.01). Analysis of baroreflex function in anesthetized rats revealed a significant impairment in the STZ group when compared to CTL. Particularly, STZ‐treated rats were unable to increase compensatory HR at lower blood pressures (at 50 mmHg: CTL, n=5, 369 ± 13 bpm vs. STZ, n=7, 315 ± 14 bpm; p≤0.05). STZ rats also had a lower baroreflex gain indicating reduced sensitivity to blood pressure fluctuations (p≤0.001). Additionally, recordings of splanchnic sympathetic nerve activity (SSNA) in a subset of rats identified reduced nerve activity during low blood pressure in the STZ group (∫SSNA at 50 mmHg: CTL, n=3, 0.3 ± 0.03 mV.s vs. STZ, n=3, 0.17 ± 0.02 mV.s; p≤0.05). There was no difference between groups at higher blood pressures (150 mmHg). Within the STZ group, HRV was significantly increased only during PE infusion (SDNN, p≤0.05; SD1, p≤0.05; SD2, p≤0.05). Interestingly, the change in HR following blockage of sympathetic or parasympathetic input was not different between groups. Also intrinsic HR and the blood pressure change to ganglionic blockage were similar between STZ and CTL rats.ConclusionsOur study provides the first insight into the pathological influence of AD on baroreflex function. We showed that STZ rats exhibit lower HR and reduced sympathetic output in response to low blood pressure. These results provide the basis for identifying the mechanism behind orthostatic hypotension in AD patients.Support or Funding InformationATSU biomedical grant (JCE) and seed money (TDO)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Prostaglandin EP3 receptor‐expressing neurons in the preoptic area are activated by ambient heat exposure
Authors: Nakamura Yoshiko , Nakamura Kazuhiro 
Published: June 2021

The preoptic area (POA) receives cutaneous warm and cold inputs ascending through the lateral parabrachial nucleus, and local neural circuits in the POA function as a center for body temperature regulation. The cutaneous warm inputs to the POA can activate inhibitory neurons therein, which then inhibit the sympathoexcitatory efferent neural pathways that otherwise drive cold‐defensive thermogenesis and cutaneous vasoconstriction. The POA also contains warm‐sensitive neurons that have intrinsic warm sensitivity to monitor body core (local brain tissue) temperature and thereby determine the basal tone of the thermoregulatory efferent signaling, although the histochemical or molecular identity of warm‐sensitive neurons remains unknown. The prostaglandin EP3 receptor, a Gi‐coupled inhibitory receptor of prostaglandin E2, a pyrogenic mediator, is expressed in POA neurons, and an action of prostaglandin E2 on these neurons triggers fever likely by disinhibiting sympathoexcitatory neurons in the dorsomedial hypothalamus and the rostral medullary raphe region. To determine whether EP3 receptor‐expressing POA neurons contribute to thermal homeostasis in warm and cold conditions, in this study, we exposed rats to a heated (36°C), control (24°C) or cold (4°C) environment for two hours and examined activation of EP3 receptor‐expressing POA neurons by double‐immunostaining for EP3 receptors and c‐Fos, a marker for neuronal activation. Heat‐exposed rats exhibited a significant increase in c‐Fos‐positive cells in EP3 receptor‐expressing POA neurons, compared with rats exposed to the control environment. However, cold exposure had no significant effect on the number of c‐Fos‐positive cells in EP3 receptor‐expressing POA neurons, compared with control exposure. These results suggest that EP3 receptor‐expressing POA neurons are activated in hot environments due to its intrinsic warm sensitivity and/or by cutaneous warm inputs and function for heat defense, as well as fever development after infection.Support or Funding InformationJSPS KAKENHI 17K08568, 23790271 & 26860159 (YN), 16H05128, 15H05932 & 26118508 (KN); AMED JP18gm5010002 (KN); Hori Sciences and Arts Foundation (YN)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Water deprivation enhances the hypercapnic ventilatory response in rats
Authors: Nakai Larissa Bonassi , Silva Elaine Fernanda , Menani José Vanderlei , Colombari Débora Simões Almeida , Zoccal Daniel Breseghello , Colombari Eduardo 
Published: June 2021

Behavioral, neuroendocrine, autonomic and cardiovascular adjustments are triggered during water deprivation. However, the effects of water deprivation on ventilation remain to be determined. Herein, we evaluated the pulmonary ventilation after 48 h of water deprivation in male Holtzman rats (280–300 g) under unanesthetized conditions. Control rats (n=7) had continuous access to tap water and food, whereas water‐deprived (WD, n=6) rats had water, but not food removed for 48 h before the experiments. Rats were placed in whole‐body plethysmographic chamber (5 L) to measure the respiratory frequency (fR), tidal volume (VT) and minute ventilation (VE) under baseline condition (room air) and during hypercapnia (7% CO2 for 5 min). After the experiments, animals were decapitated for blood collection. WD rats had an increase in serum osmolality (307 ± 1 mOsmol/kg of water, vs. control: 297 ± 1 mOsmol/kg of water; p<0.05) and sodium concentration (148 ± 0.6 mmol/L, vs. control: 141 ± 0.5 mmol/L; p<0.05). WD rats exhibited increased VT (9.7 ± 0.5 mL.kg−1, vs. control: 7.7 ± 0.3 mL.kg−1; p<0.05) but reduced fR (76 ± 2 breaths.min−1, vs. control: 103 ± 7 breaths.min−1; p<0.05) compared to controls. As a result, baseline VE (746 ± 54 mL.kg−1.min−1, vs. control: 799 ± 64 mL.kg−1.min−1) were similar between groups. Under hypercapnia, the response of increases in VT were statistically similar between WD and control groups (ΔVT: 60 ± 16%, vs. control: 33 ± 7%). On the other hand, WD rats demonstrated amplified hypercapnia‐induced increases in fR (Δ: 47 ± 5%, vs. control: 19 ± 5%; p<0.05) and VE (Δ: 140 ± 35%, vs. control: 59 ± 9%; p<0.05). The results show that 48 h of water deprivation enhanced the ventilatory responses induced by hypercapnia in unanesthetized rats.Support or Funding InformationFAPESP; CNPqThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The amplitudes of miniature excitatory postsynaptic currents in NTS neurons from female rats vary as a function of the estrus cycle
Authors: Jia Shuping W , MIfflin Steve 
Published: June 2021

Very little information exists regarding how glutamatergic transmission within the nucleus of the solitary tract (NTS) of females might vary as a function of the estrus cycle. Spontaneous miniature excitatory postsynaptic currents (mEPSCs) were recorded in caudal NTS slices (250μM thick) superfused with TTX (1 um) and gabazine (25 um) under voltage clamp. Female rats were studied at different stages of the estrus cycle determined by vaginal smear and the number of neurons studied at each stage of the estrus cycle is as follows: estrus n=16; metestrus n=14; diestrus n=22. Male rats (n=33) were also studied for comparison. All mEPSCs were blocked by superfusion of the slice with CNQX (10 um). The amplitude of mEPSCs was significantly lower in diestrus (16.53 ± 1.01 pA) compared to estrus (23.30 ± 2.12 pA), metestrus (19.95 ± 1.13 pA), and males (20.49 ± 1.29 pA) (all p<0.035). The frequency of mEPSCs did not vary across the estrus cycle in females however mEPSC frequency was significantly lower in males (2.74 ± 0.28 Hz) compared to estrus (4.23 ± 0.63 Hz, p=.010) and metestrus (4.34 ± 0.61 Hz, p=.005). The frequency of mEPSCs did not differ between males and females in diestrus (3.68 ± 0.54 Hz, p=.085). mEPSC rise time did not differ between the 3 female groups and males (all p>.111). mEPSC decay time was significantly greater in estrus (9.00 ± 0.75 ms) compared to males (7.50 ± 0.39 ms, p=.038) but decay time during estrus did not differ from that in metestrus (7.58 ± 0.61 ms) and diestrus (7.59 ± 0.41 ms) (both p>.088). These results suggest that glutamatergic transmission in NTS neurons in female rats can vary as a function of the estrus cycle. During diestrus plasma estrogen levels are rising and during diestrus we observed mEPSCs with amplitudes lower than during other phases of the estrus cycle or in males. This suggests that estrogen may have a post‐synaptic effect that reduces NTS neuronal responses to glutamatergic inputs. Preliminary whole cell recordings from 3 NTS neurons in a brain slice from estrogen receptor alpha‐td tomato reporter mice lend support to this interpretation as superfusion of the slice with 100 nm 17β‐estradiol reversibly reduced mEPSC amplitude from 19–29%.Support or Funding InformationThis work was supported by HL088052This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Sex‐Dependent Differences in NMDA and GABA Receptor Subunits in the Rat Rostral Ventrolateral Medulla
Authors: Mueller Patrick J , Azar Toni A , Fyk‐Kolodziej Bozena E 
Published: June 2021

The cardioprotective effects of female hormones/female sex are well‐described. In particular, several studies demonstrate the importance of female hormones on regulation of sympathetic outflow, a primary contributor to normal blood pressure as well as cardiovascular disease. Protective effects of ovarian hormones may include actions in the rostral ventrolateral medulla (RVLM), a brain region critical to sympathetic outflow and blood pressure. However, the time course and mechanisms by which sex‐differences contribute to excitation and inhibition of RVLM neurons are not fully elucidated; particularly in sexually immature animals, which lack higher levels of reproductive hormones. Therefore, we hypothesized that in the presence of lower levels of reproductive hormones, sexually immature females may exhibit increased glutamate (excitatory) receptors and decreased GABAA (inhibitory) receptors, indicative of an excitatory profile in the RVLM. To test our hypothesis, we obtained brain punches from the RVLM of four week old, male and female Sprague‐Dawley rats (n=3 ea), and processed them for western blotting. The NMDA (NR1) subunit was expressed in the RVLM of both sexes, but was expressed at a higher level in females compared to males (1.10±0.08 vs. 0.65±0.10 protein/GAPDH, respectively). The GABAAα1 subunit was also expressed in the RVLM of both sexes, but was expressed at lower levels in females compared to males (0.61±0.08 vs. 0.79±0.10 protein/GAPDH, respectively). These results suggest that prior to the onset of sexual maturity, a lower level of female hormones may increase the relative excitability of the RVLM and lead to greater sympathoexcitation in females compared to males. These experiments illustrate the importance of studying the time course and level of sexual maturity of animals in studies involving the influence of reproductive hormones. We are currently performing in vivo studies to examine the functional correlates of a greater excitatory profile in the RVLM of female rats, and to what extent sexual maturation influences the RVLM in both sexes.Support or Funding Information(HL096787‐07; AHA25810010)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Sympathetic Changes through the Menstrual Cycle are Absent in Women with Diabetes
Authors: Joshi Hitesh , McGaugh Sarah , Edgell Heather 
Published: June 2021

BackgroundGlycemic variability (GV) can contribute to autonomic dysfunction in diabetes (Jaiswal et al. 2014), and autonomic dysfunction can be apparent as early as childhood (Metwalley et al. 2018). In women with diabetes, GV can differ throughout the menstrual cycle where hyperglycemia and decreased insulin sensitivity are often present in the luteal phase (Brown et al. 2015). Therefore, we investigated the role of the menstrual cycle in autonomic control in women with diabetes.MethodsWomen with diabetes (n=7; age 23.6 ± 1.0years; BMI 24.4 ± 1.1kg/m2) were tested in the early follicular (EF; day 2–5) and mid‐luteal (ML; day 18–24) phases of the menstrual cycle. Blood glucose was 8.6 ± 1.1mmol/L in the EF phase and 8.1 ± 0.7mmol/L in the ML phase (P=0.71). Trials included resting heart rate variability (HRV), paced deep breathing, Valsalva, and 10 minutes of 70‐degree upright tilt. Heart rate (HR), stroke volume index (SVi), and mean arterial pressure (MAP) were measured. Frequency domain analysis of HRV was conducted on 5 minutes of resting ECG (low frequency power (LF) and high frequency power (HF)).ResultsThe expiration to inspiration HR ratio during paced deep breathing (EF: 1.40 ± 0.06, ML: 1.43 ± 0.05, P=0.39) and the Valsalva HR ratio (EF: 2.29 ± 0.16, ML: 2.16 ± 0.13, P=0.48) were similar between the phases. During the Valsalva maneuver, the increase in MAP from Phase II minimum to the end of Phase II was similar between phases (EF: +18.6 ± 3.8mmHg, ML: +18.4 ± 1.5mmHg, P=0.64). Upright tilt resulted in higher HR (P=0.005) and lower SVi (P=0.011) with no interaction effects between tilt and menstrual phase (P≥0.64). The maximum HR response to tilt was similar between the phases (EF: 101.2 ± 5.7bpm, ML: 99.5 ± 5.9bpm, P=0.69). There were no differences between phases in resting heart rate variability (LF(nu): EF: 37.5 ± 6.0, ML: 40.2 ± 6.8, P=0.68; HF(nu): EF: 45.0 ± 8.3 ML: 58.0 ± 6.3, P=0.66).ConclusionAbidi et al. (2017) found a strong tendency for a greater MAP response to Valsalva in the ML phase compared to the EF phase in healthy women. They also found higher heart rate and cardiac output in the ML phase compared to the EF phase throughout 10min of standing supporting greater sympathetic output in the ML phase. Further, in healthy participants, Brar et al. (2015) and Carter et al. (2013) found higher LF control of HR and higher resting muscle sympathetic nerve activity in the ML phase, respectively. Therefore, we suggest that the expected increase of sympathetic activity in the ML phase is absent in women with diabetes.Support or Funding InformationFaculty of Health, York University Canadian Foundation for Innovation ‐ Infrastructure Operating Fund Natural Sciences and Engineering Research Council of CanadaThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Renal Sensory Nerves Increase Blood Pressure and Sympathetic Nerve Activity in 2‐Kidney 1‐Clip Hypertensive Mice
Authors: Ong Jason , Sved Alan F , Kinsman Brian J. , Tan Roderick J , Rush Brittney M , Carrattino Marcelo D , Stocker Sean D 
Published: June 2021

Renal denervation lowers arterial blood pressure (ABP) in multiple clinical trials and some experimental models of hypertension. These antihypertensive effects have been attributed to the removal of renal afferent nerves. The purpose of the present study was to determine whether renal sensory nerves contribute to the 2‐Kidney‐1‐Clip (2K1C) model of hypertension. 2K1C hypertension was produced in male C57B16 mice (12–14 weeks, Jackson Laboratories) by placement of a 0.5mm length of PTFE tubing (ID: 0.008” x OD: 0.014”) around the left renal artery. 2K1C mice (n=10) displayed an elevated ABP measured via telemetry (Day 0: 96 ± 1mmHg vs Day 14: 120 ± 3mmHg; P<0.01). Ganglionic blockade with hexamethonium (30mg/kg, ip) produced a greater fall in mean ABP at Day 14 vs Day 0 (Day 0: −35 ± 2mmHg vs Day 14: −57 ± 5mmHg; P<0.01). 2K1C‐clipped kidneys vs 2K1C‐unclipped kidneys had lower mass (105 ± 14mg vs 173 ± 8mg, respectively; P<0.05) and higher mRNA levels of several pro‐inflammatory cytokines (IL1B, IL2, IL10, TNFa; P<0.05). Renal afferent discharge was significantly higher in 2K1C‐clipped kidneys vs 2K1C‐unclipped vs sham mice (2K1C‐clipped: 3.4 ± 0.9 Hz vs 2K1C‐unclipped: 0.7 ± 0.3Hz vs control: 0.3 ± 0.1 Hz, n=6/group; P<0.05). Furthermore, electrical stimulation of renal afferent nerves in control mice (n=6) produced a frequency‐dependent increase in ABP (5Hz: 4 ± 1mmHg, 10Hz: 6 ± 1mmHg, 20Hz: 11 ± 2mmHg; P<0.05). These responses were eliminated after ganglionic blockade with 5mg/kg chlorisondamine (5Hz: 1 ± 1mmHg, 10Hz: 1 ± 1mmHg, 20Hz: 1 ± 1mmHg, n=4/group; P<0.05). Stimulus‐triggered averaging of SNA during stimulation of renal afferent nerves (1 Hz, 200uA) revealed significant (P<0.05, n=4/group) increases in splanchnic (179 ± 11%), renal (195 ± 15%), and lumbar (167 ± 9%) SNA. Interestingly, the latency to the peak SNA (142 ± 10ms) suggests supraspinal pathways mediate the sympathoexcitatory response. Finally, both total renal denervation (10% phenol) or selective denervation of renal afferent nerves (periaxonal application of 33mM capsaicin) at time of clipping resulted in lower ABP than 2K1C mice at Day 14 (2K1C: 120 ± 3mmHg, phenol: 106 ± 3mmHg, capsaicin: 108 ± 3mmHg, n=6–10/group; P<0.05). These findings suggest 2K1C hypertension depends on renal sensory nerves and elevated SNA via supraspinal pathways.Support or Funding InformationNIH grant HL113270, AHA Undergraduate Research FellowshipThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.