bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effects of Oral Contraceptive Use on Ergoreflex control of Blood Pressure and Heart Rate during Steady‐State Cycling in Healthy, Young Women
Authors: Chantigian Daniel , Asirvatham‐Jeyraj Ninitha , Keller‐Ross Manda 
Published: June 2021

BackgroundErgoreflex, activation of group III/IV skeletal muscle afferents, is an important regulator of mean arterial pressure (MAP) and heart rate (HR) during exercise. Oral Contraceptive (OC) use in women has been shown to increase resting BP, but the effect of OC use on the ergoreflex is unclear.ObjectiveDetermine if OC use causes an exaggerated MAP and HR response with ergoreflex activation in young, healthy women.MethodsTwelve healthy women (mean ± SD; 24±2 yrs, 7 taking OCs) attended 2 experimental sessions; one during early follicular (low estrogen, days 1–4) and one during ovulation (high estrogen, days 10–14). Each session included 1) 3 minutes of light‐intensity steady‐state cycling (60 W at 65–70 rpm) and 2) 3 randomized, subsystolic circulatory occlusions applied bilaterally to the proximal thigh at 20, 60, and 100 mmHg of pressure to increase activation of group III/IV skeletal muscle afferents (ergoreflex). Occlusions lasted 2 min and were separated by 5 min of deflation with 2 min of recovery at the end (rest). MAP and HR were continuously monitored via non‐invasive blood pressure (Nexfin, Edwards Lifesciences, Irvine, CA) and a 3‐lead ECG (AD Instruments, Colorado Springs, CO), respectively.ResultsData did not differ significantly between women in the follicular or ovulatory phases; thus, the ovulatory phase data was used for comparisons. HR increased from rest to exercise more with women in the ovulatory phase (68±14 to 130±12 bpm) as compared with women taking OCs (69±14 to 112±10 bpm, exercise *OC interaction: p=0.02). However, HR increased from baseline exercise with vascular occlusion (condition: p<0.01) similarly in women in the ovulatory phase and women taking OCs (20 mmHg: 3±9% vs. 1±2%, 60 mmHg: 4±3% vs 8±4%, and 100 mmHg: 9±17% vs. 20±8% respectively, condition*OC interaction: p=0.14). MAP increased from rest to exercise similarly in women in the ovulatory phase (83±8 to 92±14 mmHg) as compared with women taking OCs (88±7 to 92±8 mmHg, exercise*OC interaction: p=0.08). MAP increased from baseline exercise with vascular occlusion (condition: p=0.01) similarly in women in the ovulatory phase as compared with women taking OCs (20 mmHg: 7±19% vs. 2±8%, 60 mmHg: 15±16% vs. 2±9%, and 100 mmHg: 8±18% vs. 28±19%, condition*OC interaction: p=0.20).ConclusionPrevious studies have implicated that blood pressure tends to be greater with OC use, this study suggests that OCs do not cause an exaggerated increase in MAP during exercise or activation of group III/IV afferents. OCs attenuate the HR response to exercise, but does not appear to affect the HR response to group III/IV afferent activation.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The response of vagal motoneurons to brainstem oxytocin stimulation depends on sex and stress levels.
Authors: Jiang Yanyan , Zimmermann Julia , Travagli R. Alberto 
Published: June 2021

Stress maladaptation plays a pivotal role in the development and exacerbation of functional gastrointestinal disorders (FGID), including impaired gastric emptying and decreased gastric motility, both of which are more prevalent in women. The prototypical anti‐stress hormone, oxytocin (OXY), has been shown to modulate GI tone and motility via vagal pathways. We have shown previously that in naïve male rats, OXY modulates the critical GABAergic synapse projecting to gastric‐projecting preganglionic vagal (DMV) neurons only after pharmacological increase of cAMP levels by forskolin or CRF pretreatment, suggesting a stress‐induced plasticity of brainstem vagal neurocircuits.The aim of this study was to test the hypothesis that the response of vagal motoneurons to brainstem oxytocin application depends on sex and stress adaptation or resilience. Age‐matched male and female SD rats were subdivided in the following groups: i) control; ii) chronic repetitive homotypic (restraint) stress, rats in this group show adaptation to stress; iii) chronic repetitive heterotypic (restraint, forced swim, water avoidance and cold) stress, rats in this group do not show adaptation to stress. Female rats were further subdivided according to their estrogen levels (high: pro‐estrus and estrus; low: meta‐ and di‐estrus). Following 5‐days of stress, whole cell patch clamp recordings were made from thin brainstem slices to examine GABAergic miniature inhibitory postsynaptic currents (mIPSCs) in medial, presumably gastric‐projecting, DMV neurons.Our results, see table, indicate that 1) in male rats OXY modulated inhibitory neurotransmission only in stressed rats; 2) in female rats, OXY modulated inhibitory neurotransmission independently of estrogen or stress load. 3) OXY effects on mIPSC frequency, however, is different when rats are exposed to heterotypic stress load. Taken together, our data support the hypothesis that the response of vagal motoneurons to brainstem oxytocin stimulation depends on sex and stress levels and suggest that, independently of estrogen or stress, female rats have a response similar to that of stressed males.Support or Funding InformationNIH DK 55530This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Brain‐Heart Coupling Response during Auditory Startle
Authors: Wang Xiaoni , Luan Yewei , Dang Shijie , Li Mengjun , Zhang Jianbao 
Published: June 2021

ObjectivePrevious clinical observations have revealed the possible relation between auditory startle stimulation and susceptibility to ventricular fibrillation, which cause 10% of sudden deaths without structural abnormalities of the heart. The objective of the study was to investigate the impact of auditory startle on time‐varying autonomic reactivity and cerebral‐cardiovascular coupling.MethodsStartle reflexes in the study were induced by auditory stimulation of 100 db white noise lasting 100 ms. 25 healthy male subjects were recruited. Electrocardiogram (ECG), beat‐to‐beat blood pressure and electroencephalography (EEG) were measured simultaneously and continuously during baseline and startle task. Further, RR intervals (RRI), systolic and diastolic blood pressure (SBP, DBP) and mean magnitude of auditory‐evoked alpha and beta potential oscillations were calculated. Continuous wavelet transformation of RRI was used to describe the time‐variant patterns of autonomic neural activities. Pearson correlation and cross‐correlation were used to estimate the coupling between evoked oscillation and RRI, as well as between RRI and SBP.ResultsAcute response of auditory startle was characterized by instant heart rate (HR) (0–1.5 s) decrease and subsequent (1.5–4 s) increase, tardive SBP elevating (3.5–7 s) and recovery (>7 s), accompanied with acute auditory‐evoked alpha and beta potential oscillations. Magnitude of evoked alpha oscillations in electrode FP1 and FP2 coupled with decreased HR in 0–1.5 s and increased HR (1.5–4 s) coupled with evoked beta oscillations magnitude in FT8, T8 and TP8. Moreover, directional influence from RRI to SBP was disrupted while baroreflex was enhanced in startle reflex. Therefore, it can be indicated that auditory startle evoked excitation of cochlear nerve is transmitted ascendingly into brainstem and affects cardiovascular system through three pathways: 1) inducing the descending activation of spinal sympathetic centers; 2) a further auditory radiation of ventral medial prefrontal cortex (vMPFC), which is related to parasympathetic activation; and 3) anterior and posterior temporal lobe, which is the cardiovascular sympathetic center. The excitement of three pathways above occurs almost simultaneously. However, the fact that parasympathetic nerves exert their effects on cardiovascular system more rapidly than sympathetic nerves accounts for the earlier decrease and subsequent increase of HR. Coupling of RRI and SBP predominantly contributes to HR and SBP changes after 5 s.ConclusionThe results of the study confirmed the connection of cortex and cardiovascular system. Acute startle related cardiovascular responses is coupled with the startle evoked EEG oscillations while subsequent responses may be induced by RRI and BP coupling.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Consequences of postnatal myo‐inositol supplementation on respiratory control and nucleus tractus solitarius (nTS) neurons
Authors: Mayer Catherine A. , Difiore Juliann M. , MacFarlane Peter M. 
Published: June 2021

Myo‐inositol is a naturally occurring sugar derivative formed endogenously from the breakdown of glucose; it is also found in a variety of foods including breast milk and is commercially available as a nutritional supplement. Serum levels of myo‐inositol in infants decrease naturally over the first few postnatal weeks; prior studies in preterm infants have demonstrated improved pulmonary function, reduced incidence of respiratory distress, and increased survival rates following myo‐inositol supplementation. In support of a potential beneficial effect of myo‐inositol supplementation on respiratory control, we have shown previously that myo‐inositol treatment over the first 2 postnatal weeks enhances the acute hypoxic ventilatory response (HVR). In the present study, we tested the hypothesis that the enhanced HVR following myo‐inositol treatment would be associated with increased excitability of neurons within the area of brainstem chemoafferent integration, the nucleus tractus solitarius (nTS). Mouse pups received subcutaneous injections of myo‐inositol (80 mg/kg/day) for the first two postnatal weeks. Whole cell patch clamp recordings were then used to examine the excitatory properties of nTS neurons monosynaptically connected to the solitary tract. Compared to saline treated mice, myo‐inositol exposure increased the rheobase and the failure rate of nTS neurons, and decreased the paired pulse ratio following 20 Hz stimulation. Spontaneous activity (EPSC frequency, area, rise time, decay time), and basic neuronal properties (membrane resistance, capacitance, resting membrane potential) did not differ between groups. In conclusion, and contrary to our hypothesis, the enhanced HVR following postnatal myo‐inositol treatment was associated with decreased excitability of nTS neurons. We speculate the reduced nTS neuron excitability may be a compensatory response to increased chemoafferent (presumably the carotid body) inputs during hypoxia. These data may be important to our understanding of how myo‐inositol supplementation could influence development and function of brainstem respiratory neural control regions and may have implications for the pathophysiology of various respiratory morbidities in preterm infants.Support or Funding InformationThe Gerber FoundationThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Chemoreflex Responses to LPS Exposure During a Critical Window of Development in the in situ Arterially Perfused Working Heart Brainstem Preparation
Authors: Kola Gjinovefa , Chadha Priyal , Mayer Catherine A. , Dick Thomas E. , Dutschmann Mathias , Lewis Stephen J. , MacFarlane Peter M. 
Published: June 2021

The second week of postnatal life represents a critical window of brainstem cardio‐respiratory neural development in rats. We showed previously that endotoxin (lipopolysaccharide, LPS) exposure during this critical period of development (specifically at P10 days of age) attenuated the acute hypoxic ventilatory response and increased brainstem cytokine mRNA expression; these effects of LPS were also associated with an unexpected increase in mortality. These data suggest there may be a critical window of development during which the (cardio)‐respiratory control system exhibits a heightened vulnerability to inflammatory challenges. The potential impact of LPS exposure on neural control of cardio‐respiratory function during this critical window of development is unknown. We used the in situ arterially perfused working heart brainstem preparation to investigate how LPS affects central nervous control of respiratory and autonomic function in P10 rats. Two hours after an intraperitoneal injection of LPS (0.1mg/kg, n=24), rats were surgically prepared for chemoreceptor mediated sympathoexcitation by measuring phrenic, vagal, and thoracic sympathetic nerve responses to an intra‐arterially injection of sodium cyanide (75 μl, 0.03% NaCN). Rats were also cannulated for measurements of heart rate and arterial/perfusion pressure. Compared to saline treated controls, LPS decreased baseline phrenic nerve burst frequency by 27% and increased vagal nerve activity by 76% (peak amplitude). Baseline thoracic sympathetic nerve activity, heart rate and arterial perfusion pressure were similar between treatment groups. Although NaCN increased respiratory frequency and vagal nerve activity in both groups, the frequency response was attenuated by 35% in LPS treated rats. The magnitude of the thoracic sympathetic nerve and bradycardic response to NaCN was not affected by LPS treatment. These data indicate that LPS depresses baseline respiratory network function and impairs vital respiratory response to arterial chemoreceptor activation. In conclusion, the present data suggest that inflammatory challenges during a critical period of development trigger potentially fatal instabilities in respiratory network function.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Aspects of Respiratory Control in the Dystrophin‐deficient mdx Mouse
Authors: Burns David P. , O'Driscoll Eabha , Edge Deirdre , Lucking Eric F. , O'Halloran Ken D. 
Published: June 2021

Duchenne muscular dystrophy (DMD) is a fatal neuromuscular disease characterised by skeletal muscle weakness which extends to the respiratory musculature. Although deficits in the diaphragm muscle of dystrophin‐deficient mdx mice are well described, there is a paucity of information pertaining to central control of breathing in dystrophinopathies. We have previously reported hypoventilation in mdx mice with reserved capacity to increase ventilation in response to chemoactivation (Burns et al., 2017). Systemic and muscle inflammation are reported in mdx mice and human DMD. We sought to examine aspects of respiratory system control in the mdx mouse model of DMD including electrical activity of the diaphragm muscle and markers of inflammation in putative phrenic motor nuclei.Young adult (8 week old) wild‐type (WT) and mdx mice were studied. Inspiratory (Ti) and expiratory (Te) durations were assessed in conscious WT and mdx mice using whole‐body plethysmograpghy. Diaphragm EMG activity was assessed in WT and mdx mice using fine concentric needle electrodes in anaesthetised spontaneously breathing mice. Basal EMG and responsiveness to chemoactivation were determined. Diaphragm muscle function was examined ex vivo. Cervical spinal cord (C3–C5 region) segments of WT and mdx mice were examined for immunohistochemical and gene expression analyses.Poincaré analysis of Ti and Te revealed no evidence of perturbed respiratory rhythm in young mdx mice based on short‐ and long‐term variability of breathing. Diaphragm muscle force was severely depressed in mdx diaphragm within the frequency range of both ventilatory and airway protective behaviours. Mdx diaphragm had potentiated EMG activity during chemoactivation compared to WT mice. Dystrophin mRNA is expressed in the C3–C5 region of WT spinal cords and expression is significantly reduced in mdx mice, with no indication of altered inflammatory gene expression. Putative phrenic motornuclei in mdx mice had unaltered expression of microglia and astrocytes compared to WT.Our study revealed a potentiated neural drive to breathe in mdx mice during chemoactivation suggesting compensatory neuroplasticity facilitating respiratory motor output. Although systemic and muscle inflammation are present in mdx mice, there is no evidence of neuroinflammation in the cervical spinal cord (C3–C5) of young mdx mice. If neuroplasticity is a feature of DMD, it may be possible to boost motor facilitation of breathing through safe interventions and thus preserve or limit deficiencies in respiratory capacity.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Differential Activation of Respiratory Muscles during Lower Thoracic High Frequency Spinal Cord Stimulation (HF‐SCS)
Authors: Kowalski Krzysztof E. , Romaniuk J Richard , Pawlowski Gary , DiMarco Anthony F. 
Published: June 2021

ObjectiveLower thoracic HF‐SCS (500 Hz, 1 mA) applied via a single stimulating electrode located on the dorsal surface of the spinal cord at the T9 level results in large positive airway pressures consistent with marked expiratory muscle activation. The purpose of the present study was to evaluate the effects of lower thoracic HF‐SCS on the ventral surface at this spinal level.MethodsIn 4 anesthetized dogs, HF‐SCS was applied via a stimulating electrode (4 mm disc) positioned on the ventral surface of the spinal cord at the T9 level. Airway pressure generation was monitored before and following spinal sections at the C8 (to eliminate potential diaphragm activation) and subsequently at the T6 (to eliminate potential intercostal muscle activation) levels.ResultsHF‐SCS (500 Hz, 1 mA) on the ventral surface, results in inspiratory airway pressure generation of 40 ± 3 cmH2O. Following complete C8 spinal section, HF‐SCS results in a significant reduction in negative airway pressure generation to 14 ± 1 cmH2O (p<0.05). Subsequent section at the T6 level, HF‐SCS results in a positive airway pressure of 10±1 cmH2O (p<0.05 when compared to before either section).ConclusionIn contrast to dorsal stimulation, lower thoracic ventral HF‐SCS (500 Hz, 1 mA), at T9 results in activation of pathways with connections to both the phrenic and inspiratory intercostal motoneuron pools resulting in the generation of the large negative airway pressures and minimal expiratory muscle activation. Under the experimental conditions of this study, neuronal pathways with connections to the inspiratory and expiratory motoneuron pools are each limited anatomically to specific regions of the spinal cord. These anatomic differences allow for separate activation of the inspiratory and expiratory muscles to restore function.Support or Funding InformationSupport: Merit Review Award I01‐RX‐001488 from the U.S. Department of Veterans Affairs, Rehabilitation Research and Development Service.Disclosure: Dr. DiMarco holds two U.S. patents for technology related to the content of this abstract: Method and Apparatus for Electrical Activation of the Expiratory Muscles to Restore Cough (5,999,855) and Bipolar Spinal Cord Stimulation to Activate the Expiratory Muscles to Restore Cough (8,751,004).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Novel Mouse Model of a Human Mutation in NKCC1 Confirms its Mistargeting in Epithelia
Authors: Koumangoye Rainelli , Omer Salma , Delpire Eric 
Published: June 2021

A 15‐year old patient with complete gastrointestinal and bladder failure, endocrine insufficiencies, and orthostatic intolerance carries a de novo mutation in SLC12A2, the gene encoding the Na‐K‐2Cl cotransporter‐1 or NKCC1. The 11 bp deletion leads to truncation of the cytosolic COOH‐terminal tail of the cotransporter making it non‐functional. Expression of the mutant transporter increases the amount of dimerization, suggesting the possibility that the mutant transporter might exert dominant‐negative effects on the wild‐type transporter. In polarized MDCK cells grown on permeable filters or in 3‐D culture cysts, most of the mutant transporter signal is observed on the apical membrane, in contrast to the basolateral expression of wild‐type cotransporter. The mutant transporter affects the formation of MDCK cysts, as we observed the presence of multiple lumens, as opposed to single lumen formation with wild‐type cells. The mutant transporter also causes trafficking of the wild‐type cotransporter to the apical membrane.To assess the relevance of this observation in vivo, we created a mouse model that recapitulates the human mutation. Using CRISPR/cas9, a guide RNA that targets cas9 to exon 22 of the Slc12a2 gene, and a repair oligonucleotide that deletes 11 bp from the exon, we successfully generated a female founder animal that carried the designed mutant allele in addition to a non‐homologous end joining mutation in the second allele. After one backcross that segregated the two alleles, the line was further established by backcrossing for 2 additional generations in C57BL/6J. This mouse now carries the 11 bp deletion mutant allele and a wild‐type allele. We examined the expression of NKCC1 in the salivary gland and the intestine, two Cl− secreting epithelia where the wild‐type cotransporter is typically expressed on the basolateral membrane. In both tissues, intense apical staining was observed, confirming the data obtained with MDCK cells. Preliminary studies indicate that the mouse has no overt adverse phenotype, although the mouse lives in a pathogen‐free barrier facility and has not been challenged.In conclusion, our data demonstrate that expression of a truncated Na‐K‐2Cl cotransporter causes mistargeting of the wild‐type cotransporter to the apical membrane of Cl− secreting epithelia and affects proper lumen formation in MDCK cysts. These observations may explain the multisystem dysfunction that is observed in the patient.Support or Funding InformationSupported by NIH grants R21GM118944 and 1RO1DK093501.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.