bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic electrical stimulation of the carotid sinus enhances the sensitivity of baroreflex‐mediated heart rate regulation
Authors: Iliescu Radu , Irwin Eric D. , Cates Adam W. , Georgakopoulos Dimitrios , Rossing Martin A. , Lohmeier Thomas E. 
Published: June 2021

Prolonged activation of the baroreflex (PBA) by electrical stimulation of the carotid sinus stimulates the afferent limb of the baroreflex producing sustained reductions in sympathetic activity, average daily blood pressure (BP) and heart rate (HR). We used the sequence method to determine if PBA impairs dynamic baroreflex control of HR. Spontaneous, consecutive, parallel changes in systolic BP (SBP, >1 mmHg) and pulse interval (PI, >5msec) were determined 18 hours/day in 6 normotensive dogs during two weeks of PBA. During PBA at moderate intensity, average systolic BP and HR decreased by 27±3mmHg and 9±2bpm along with sustained reductions in the variability of beat‐to‐beat SBP (19±1 to 14±1) but not PI. The occurrence of non‐baroreflex sequences (opposite changes in SBP and PI) decreased from 32±3 to 18±4 / 10 4beats after 2 weeks of PBA, presumably a consequence of depressed sympathetic activity. In contrast, the number of baroreflex sequences of ≥ 4 beats remained constant (551±118/ 10 4beats) during PBA as baroreflex sensitivity increased ~ 2 fold (Figure). All parameters returned to control levels after 1 week of recovery. These data indicate that PBA chronically suppresses sympathetic activity, increases baroreflex sensitivity and preserves baroreflex HR regulation.image
Neurotrophins induce NO generation in pulmonary artery endothelial cells
Authors: Meuchel Lucas W , Thompson Michael A , Pabelick Christina M , Prakash Y S 
Published: June 2021

Traditionally associated with neuronal structure and function, neurotrophins (NTs; e.g. brain derived neurotrophic factor (BDNF), neurotrophin‐3 (NT3 )) and their receptors (tropomyosin related kinase; Trk) have been found in the adult lung, pulmonary artery and airway; however, their roles remain unclear. Based on previous findings of pulmonary hypertension in NT receptor knockout mice, we hypothesized that NTs induce production of nitric oxide (NO) in pulmonary endothelial cells (EC), thereby modulating pulmonary vascular tone. In human pulmonary artery EC loaded with the NO sensitive fluorescent dye DAF‐2, 50 ƒÝM ATP and both BDNF and NT3 (1 and 10 nM) acutely (<5 min) and substantially in increased fluorescence levels. Addition of the NO scavenger PTIO reversed these changes. Specificity of DAF2 for NO was tested using the short‐acting NO donor MAHMA‐NONOate, and the nitrous oxide donor Sulfa‐NONOate. Furthermore, NT‐induced elevation in NO was significantly reduced by pre‐exposure to the tyrosine kinase inhibitor K252A (100 nM, 20 min), the NOS inhibitors L‐NMMA or L‐NAME, and the Ca2+ chelator BAPTA. Acute NT exposure also increased eNOS phosphorylation. These results indicate that NT¡¦s such as BDNF and NT3 can acutely modulate endothelial NO production, and may contribute to pulmonary vasodilation.Supported by NIH grants HL088029, (YSP), HL56470 (YSP), and Mayo Graduate School (LWM).
Diaphragm and intercostal neuromuscular plasticity following C2 spinal hemisection injury (C2HS)
Authors: Gill Luther , Lee Kun‐Ze , Smith Barbara K , Vandenborne Krista , Reier Paul J , Fuller David D 
Published: June 2021

C2HS transiently paralyzes the ipsilateral (IL) hemidiaphragm (HD) and induces compensatory increases in contralateral (CL) HD activity. In ongoing experiments, we are examining how chronic C2HS in adult male Sprague‐Dawley rats influences CL HD fiber size and type, and the expression of myogenic markers. Parallel experiments are quantifying the impact of chronic C2HS on inspiratory intercostal muscle electromyogram (EMG) activity. Bilateral EMG recordings from the IL and CL HD (medial costal portion) and external intercostal muscles (5th space) were obtained in urethane‐anesthetized spontaneously breathing rats at 1–60 days post‐C2HS. Diaphragm tissue was then harvested and prepared for histological and immunohistochemical evaluation. Preliminary histological analyses indicated an increase in centrally located myonuclei in CL HD myofibers and inflammatory cell infiltration by 24 hrs post‐injury. In addition, there appears to be a reduction in the relative number of type 1 myofibers in the CL HD by 48 hours post‐injury. Robust inspiratory bursting was observed in the CL intercostal EMG of all rats. IL intercostal EMG bursting was evident as early as 24 hrs post‐C2HS, whereas IL HD EMG activity was absent even as late as 14 days post‐C2HS. We conclude that the CL diaphragm begins to remodel almost immediately following C2HS, and cross spinal pathways enable IL intercostal recovery shortly after injury.Support: NIH 1R01HD052682‐01A1, NIH T32 HD043730
Effects of topical anesthetic on the pharyngeal sensory evoked potential
Authors: Hegland Karen Wheeler , Pitts Teresa , Hegland Dustin L , Davenport Paul W 
Published: June 2021

Intact sensation to the upper airways is an integral part of safe and efficient swallowing. The initiation of the pharyngeal stage of swallowing is dependent upon sensory information, largely from mechanoreceptors located in the posterior pharyngeal wall. Degradation of sensory function in that area commonly results in dysphagia (disordered swallowing) characterized by a delay in the initiation of swallowing and discoordinated motor output. It was hypothesized that application of topical anesthetic directly to the surface of the posterior pharyngeal wall would result in quantifiable changes in the pharyngeal sensory evoked potential (PSEP) waveform. Healthy volunteers between the ages of 18 and 35 participated in the study. PSEPs were measured via 32 electrode cap (10–20 system) connected to SynAmps2 Neuroscan EEG System. Paired‐pulse air puffs were delivered to the oropharynx using a thin polyethylene tube connected to a flexible laryngoscope under two conditions. Condition 1 consisted anaesthetized posterior pharyngeal wall, and in condition 2 a topical anesthetic (2% viscous lidocaine) was applied to the posterior pharyngeal wall. Anesthesia resulted in alterations in PSEP waveform, including significant decreased amplitude of the N100 PSEP peak. These results demonstrate the PSEP is mediated in part by mucosal receptors.Research support by NIH T32‐TNCSD
Consecutive trimix diving is associated with high incidence of gas bubbles arterialization
Authors: Ljubkovic Marko , Marinovic Jasna , Obad Ante , Breskovic Toni , Brubakk Alf O , Gaustad Svein Erik , Dujic Zeljko 
Published: June 2021

SCUBA diving is often associated with generation of venous gas bubbles (VGB) that occur during ascent and are eliminated in lungs. Some conditions, such as patent foramen ovale (PFO), bear the risk for arterialization of VGB. However, these events are rather rare in air diving protocols that adhere to standardized diving tables. The aim of this study was to examine whether VGB arterialization can be found at rest following consecutive dives with trimix (mixture of oxygen, helium and nitrogen), which is increasingly being used among divers. Seven male divers performed three dives in consecutive days with diving depths ranging from 63–65 m. VGB were monitored by ultrasound for 90 minutes after surfacing and graded on a scale from 0–5. These profiles produced a significant number of VGB. Furthermore, the arterialization of VGB was detected in 5/7 divers (71%) and in 8/21 dives (38%), with only one subject having detected PFO. Additionally, mean pulmonary artery pressure was significantly increased after each dive. The arterialized bubbles did not evoke any symptoms (or decompression sickness) in any subject. These data indicate that even conservative trimix diving is associated with high incidence of gas bubbles arterialization which, although acutely asymptomatic, requires caution and investigation of potential long term consequences.Supported by the Croatian Ministry of Science and Unity through Knowledge Fund.
Limb position affects magnitude of reactive hyperemia
Authors: Clifford Philip S , Jasperse Jeffrey L , Shoemaker J Kevin 
Published: June 2021

Several studies have reported a greater blood flow response to contractions when the limb is in the dependent compared to the independent position. These results have been interpreted as evidence for a skeletal muscle pump contribution to exercise hyperemia. An alternative explanation is that there are positional differences in myogenic tone and that a given stimulus has a greater effect when the myogenic tone is enhanced. We hypothesized that the magnitude of reactive hyperemia would be greater with the limb in the dependent position. Ten healthy volunteers of both sexes participated in the study. Brachial blood flow was measured by Doppler ultrasound and blood pressure measured by Finapres. The subjects lay supine with one arm supported in two different positions – above and below the heart. Reactive hyperemia was produced by occlusion of the arterial inflow with a blood pressure cuff inflated to 200mmHg for varying durations − 0.5 min, 1 min, 2 min, 5 min in randomized order.The peak increases in blood flow were 77±11,178±24, 291±25, 398±33 ml/min above the heart and 96±19, 279±62, 550±60, and 711±69 ml/min below the heart (p<0.01). These results show that a standard stimulus (reactive hyperemia) elicits different responses depending on limb position. Furthermore, the results suggest the need to reevaluate studies employing positional changes to examine muscle pump influences on exercise hyperemia.
Effects of Exercise Training on Biomarkers of Endothelial Function and Inflammation in Coronary Artery Disease Patients
Authors: Ribeiro Fernando , Alves Alberto J , Teixeira Madalena , Miranda Fátima , Duarte José A , Oliveira José 
Published: June 2021

Purposeto assess the effects of exercise training on biomarkers of endothelial function and inflammation.Methods47 patients after acute myocardial infarction were randomized to an exercise‐training group (ETG) receiving an 8‐week aerobic exercise programme (3× per week) or to a control group (CG) receiving usual care. At baseline and after 8 weeks the circulating levels of soluble intercellular adhesion molecule‐1 (sICAM‐1) and vascular cell adhesion molecule‐1 (sVCAM‐1), C‐reactive protein (CRP), interleukin (IL)‐6 and ‐10 were assessed.ResultsETG increased the circulating levels of IL‐10. Conversely, CG did not change the inflammatory biomarkers, but increased the endothelial dysfunction (Table 1).
Changes in the inflammatory and endothelial function biomarkers [median (percentile 25th–75th)]

ETG
CG

Baseline
Final
Baseline
Final

CRP (mg/L)
1.1 (0.5–2.2)
1.4 (0.5–2.4)
0.9 (0.5–1.7)
0.9 (0.7–1.9)

IL‐6 (pg/mL)
2.5 (1.6–3.2)
3.13 (2.1–5.0)
3.6 (1.7–6.5)
3.5 (2.8–4.7)

IL‐10 (pg/mL)
5.8 (2.6–9.1)
6.36 (4.1–14.7)†
7.7 (4.4–17.2)
7.3 (2.9–10.2)

sICAM‐1 (ng/mL)
169 (143–209)
187 (154–201)
180 (147–219)
206 (169–242)†

sVCAM‐1 (ng/mL)
297 (223–377)
340 (269–418)
245 (179–304)
341 (231–424)†

Different from baseline, P<.05

ConclusionsExercise‐training revealed an anti‐inflammatory effect, expressed by the IL‐10 increase, and counteracted the endothelial function deterioration.
Spina bifida, obesity and health: A case study
Authors: Vanderbom Kerri Ayame , Azevedo John L. , Taylor Anne , Anderson Tanja , Gorter Sandy 
Published: June 2021

The purpose of the study was to assess the effects of exercise training on trained subjects with spina bifida (TSB) compared to untrained SB subjects (UTSB).Peak power output (POpeak) and VO2peak were assessed using arm ergometry. Body composition was assessed using dual x‐ray absorptiometry. Glucose tolerance was determined using an oral glucose tolerance test (OGTT) after an overnight fast.VO2peak was 33% greater in male TSB vs. UTSB (30.8 and 20.6 ml/kg/min in TSB and UTSB). Female TSB VO2peak was 43% higher in TSB compared to UTSB (24.9 and 14.2 ml/kg/min in TSB and UTSB). POpeak was 70W in the male TSB vs. 62W in the UTSB (12% increase). Female TSB, POmax was 19% greater than UTSB (60 and 48.9W). Body fat percentage was 26.6% and 36% in male TSB and UTSB. Body fat percentage was 29 and 49% in female TSB and UTSB. Fasting blood glucose in TSB was 89.5 mg/dl which is comparable to UTSB (Widman 2007).We conclude that individuals with SB respond positively to exercise training as indicated by increased VO2peak, maximum power output, and decreased body fat percentage. Cardiovascular disease is the leading cause of death for people with spinal cord dysfunction. Additionally, metabolic dysfunction is abnormally prevalent in this population. Regular exercise should be emphasized in this population. Further research is needed. Results from this study should be taken with caution due to the small sample size.
Increased intrinsic excitability of muscle vasoconstrictor sympathetic preganglionic neurones in neonatal spontaneously hypertensive rats
Authors: Paton Julian FR , Stalbovskiy Alexey O , Pickering Anthony E 
Published: June 2021

Young, spontaneously hypertensive (SH) rats show an increased level of sympathetic activity that predates the development of hypertension (Simms et al 2009 J Physiol).We have examined the properties of muscle vasoconstrictor sympathetic preganglionic neurones (MVC‐SPN) in neonatal SH and Wistar rats. Whole‐cell recordings were obtained from SPN (Wistar n=169, SH n=76; aged p9–14) in T3–4 segment of the working heart‐brainstem preparation.SPN of SH rats showed a higher firing frequency (1.7 vs 3.0Hz) and smaller AHP amplitude. When analysed by functional subgroup it was apparent that these difference were secondary to changes in the excitability of MVC‐SPN. These showed significantly higher firing frequencies (2.2 vs 3.5Hz) with increased respiratory modulation. Additionally, the SH MVC‐SPN had shorter, smaller AHPs, lower input resistances and a weaker transient rectification (IA).Voltage clamp analysis of spontaneous excitatory synaptic events in MVC‐SPN showed similar frequencies and amplitudes of EPSCs. There was a modest preponderance of large EPSCs in SH rats (>30pA, <0.3Hz) which alone did not account for the increased spike discharge.In summary, the MVC SPN of neonatal SH rats are intrinsically more excitable. These changes occur prior to, and may play a causal role in, the development of hypertension.
Central angiotensin‐converting enzyme 2 overexpression decreases blood pressure and enhances baroreflex function in mice with chronic heart failure
Authors: Xiao Liang , Gao Lie , Lazartigues Eric , Zucker Irving H 
Published: June 2021

Central angiotensin‐converting enzyme 2 (ACE2) contributes to the regulation of cardiovascular function through modulating other components of the renin‐angiotensin system (RAS) in the brain. Since chronic heart failure (HF) is associated with sympathoexcitation, impaired baroreflex function and activation of the central RAS, we hypothesized that overexpression of ACE2 decreases blood pressure (BP) and improves baroreflex sensitivity in HF. Transgenic mice overexpressing human ACE2 selectively in the brain (Syn‐hACE2) and their wild type littermates (WT) were used, both of which developed HF (ejection fraction <45%, echocardiography) four weeks after coronary artery ligation. 24‐hour BP was monitored by radiotelemetry. Compared with WT HF group, Syn‐hACE2 HF mice exhibited lower mean BP, and ameliorated the spontaneous baroreflex sensitivity (SBRS, sequence method). These data indicate a beneficial role of central ACE2 overexpression during HF, and we speculate that ACE2 overexpression attenuates the augmented sympathetic outflow through decreasing angiotensin (Ang) II and/or increasing Ang 1–7 in the brain.

WT Sham (n=5)
Syn‐ACE2 Sham (n=5)
WT HF (n=4)
Syn‐ACE2 HF (n=4)

Mean BP (mmHg)
113±3.2
113.7±5.0
109.2±4.7
88.9±4.7#

Heart Rate (bpm)
599.5±18.9
578.1.5±21.2
647.2±20.8
644.8±10.8

SBRS (ms/mmHg)
2.21±0.24
2.91±0.51
0.82±0.15*
1.80±0.19#

p<0.05 vs. WT sham;
p<0.05 vs. WT HF.
Mutation of Tyr985 of the leptin receptor differentially alters regional sympathetic activation to leptin
Authors: Harlan Shannon Marie , Morgan Donald , Dellsperger David , Myers Martin , Mark Allyn , Rahmouni Kamal 
Published: June 2021

Leptin is an adipocyte derived hormone which acts in the brain to regulate food intake and energy expenditure. Leptin action in the brain also increases sympathetic nerve activity (SNA) to several beds including brown adipose tissue (BAT) and kidney. There is mounting evidence that the distinct signaling pathways downstream of the leptin receptor (LRb) may mediate selective leptin actions. We assessed the regional SNA response to leptin in mice (l/l) that carry a point mutation in LRb at Tyr985, which is involved in ERK activation by leptin. Multifiber recording of SNA was performed under α‐chloralose anesthesia in mice equipped with intracerebralventricular (ICV) cannula. As expected in wild type mice, ICV injection of leptin (2 μg) significantly (P<0.05 vs. vehicle) increased SNA subserving BAT and kidney. In contrast, l/l mice had a significantly (P=0.005) attenuated BAT SNA response to leptin (100±38%) as compared to wild type mice (456±130%). Renal SNA responses to leptin did not differ in l/l mice (154±80%) as compared to wild type controls (143±39%; P=NS). These data demonstrate the pivotal role of leptin receptor signaling emanating from the Tyr985 in the control of thermogenic sympathetic outflow. Our data also suggest that signaling from Tyr985 of the leptin receptor is not involved in leptin‐induced renal sympathetic activation. Together, these data demonstrate selectivity in leptin action.This work was funded by a Cardiovascular Interdisciplinary Research Fellowship, HL007121 to Shannon Harlan.
Superoxide formation induced by angiotensin II in the rostral ventrolateral medulla is enhanced by high salt diet in rats
Authors: Braga Valdir A 
Published: June 2021

Here, we investigated the association of dietary salt and angiotensin II (Ang‐II) infusion on hypertension and superoxide formation in the RVLM. Male Wistar rats were subcutaneously implanted with 14‐day osmotic minipumps containing either Ang‐II (150ng/Kg/minute) or saline (0.9% NaCl). In addition, starting at 7 days before drug infusion and continuing throughout the infusion period, rats had free access to drinking water containing 0.4% or 2.0% NaCl. For ROS accumulation measurements in the RVLM, brains were harvested at 15 days of infusion and were submitted to the dihydroethidium technique. Rats that received Ang‐II + water with 0.4% NaCl (G1) became hypertensive after 14 days of Ang‐II infusion (118±5 mmHg vs 98±4 mmHg, n=9, P<0.05). Rats that received Ang‐II + water with 2% NaCl (G2) had a significantly greater hypertension compared to G1 (165±7 mmHg vs 118±5 mmHg, n=10, P<0.05). Rats treated with saline infusion + 2% NaCl‐containing water (G3) or saline infusion + water with 0.4% NaCl (G4) did not become hypertensive (99±3 vs 98±4 mmHg, n=8 and 96±5 mmHg vs 98±4 mmHg, n=7, respectively). Furthermore, administration of hexamethonium (30 mg/Kg i.v.) reduced hypertension in G1 and G2 groups. The magnitude of superoxide formation in the RVLM was G2>G1>G3=G4 (G2= 123±10 Δ %; G1= 67±9 Δ%, P<0.05; and G3=5±3 Δ%, P>0.05), normalized by the G4 group (control). We suggest that dietary salt potentiates Ang‐II‐derived superoxide formation in the RVLM, due to an increase in the inputs within the forebrain‐PVN‐RVLM axis, leading to further increases in sympathetic nerve activity, resulting in a more severe hypertension.Supported by CNPq.
Microvascular rarefaction precedes the decline in renal function in the streptozotocin (STZ)‐induced diabetic rat
Authors: Maric Christine , Flynn Elizabeth , Sawyer R Taylor , Marbury David C , Chade Alejandro R 
Published: June 2021

Diabetic nephropathy is a generalized vasculopathic condition associated with abnormal angiogenesis. The aim of the study was to correlate changes in the 3‐dimensional renal microvasculature density (MV) with changes in renal function and vascular endothelial growth factor (VEGF).The study was performed in male non‐diabetic (ND) or STZ‐induced diabetic (D) Sprague‐Dawley rats followed for 4 (4w) or 12 (12w) weeks. Renal MV density was quantified ex vivo using a 3D micro‐CT reconstruction of the kidney. Urine albumin excretion (UAE) and renal VEGF levels were measured by ELISA and glomerular filtration rate (GFR) by 125I‐[iothalamate] clearance. 4w of diabetes was associated with a 34% reduction in MV density, no changes in UAE and augmented renal VEGF levels. At 12w, the reduction in MV density was even more pronounced (75%) and correlated with increased UAE; however, renal VEGF remained unchanged.

ND
D
P value

4w
12w
4w
12w

MV density/cm2
69.3±8.8
210±40.2*
45.5±12.3
52.7±15.6#
*0.05 vs ND at 4w #0.05 vs ND at 12w $0.05 vs D at 4w

UAE (mg/day)
1.2±0.2
2.3±1.3
2.9±0.3*
6.0±1.0#,$

GFR (ml/min/kidney)
1.4±0.2
1.3±0.2
2.1±0.3*
2.2±0.4#

VEGF (ml/min/kidney)
1.5±0.07
1.7±0.2
1.9±0.2*
1.7±0.2

The study suggests a novel concept of MV rarefaction preceding the decline in renal function in STZ‐induced diabetic rats. This effect may be related to changes in renal VEGF bioavailability with progression of diabetic renal injury.
Copper transport in gill cells of Ucides cordatus, a mangrove crab
Authors: GRANADO SÁ MARINA , ORTEGA PRISCILA , ZANOTTO FLAVIA PINHEIRO 
Published: June 2021

For most aquatic animals, the gills are important site for respiration, excretion, acid‐base balance and ion regulation. The branchial epithelium is exposed to the environment, which is frequently polluted. The aim of this work was characterize copper (Cu) transport using a fluorescent dye, Phen Green, in gill cells of a mangrove crab, found in polluted regions of Brazil. The results showed that CuCl2 added in crescent concentrations (0,0.025, 0.15, 0.275, 0.55 and 1.11μM) showed the same kinetic uptake in gill cells and a strong regulation in levels of intracellular Cu, independent of Cu concentration. Verapamil and nifedipine, known to inhibit calcium channels in apical membrane, also inhibited Cu uptake. Amiloride caused a greater efflux of copper from intra to extracellular medium, and the same results were found using calcium ionophore, which creates artificial calcium channels in plasma membrane. Besides that, the gill cells were incubated in ATP, and there were no changes in copper uptake. Caffeine, on the other hand, inhibited Cu uptake. The results showed that copper uptake is dependent of calcium uptake in gill cells, regulated by Ca channels and by Na/Ca exchangers.Supported by a CNPq fellowship to MGS, Fundo Mackenzie de Pesquisa (MACKPESQUISA) and a FAPESP Grant (06/52498‐9).
Notch and transforming growth factor‐beta signaling pathways cooperatively regulate vascular smooth muscle cell differentiation
Authors: Tang Yuefeng , Liaw Lucy 
Published: June 2021

Notch and transforming growth factor‐beta (TGFβ) play pivotal roles during vascular development and the pathogenesis of vascular disease. The interaction of these two pathways is not fully understood. The present study utilized primary human smooth muscle cells (SMC) to examine molecular cross‐talk between TGFβ1 and Notch signaling on contractile gene expression. Activation of Notch signaling induced smooth muscle alpha‐actin (SM actin), smooth muscle myosin heavy chain (SM‐MHC), and calponin1, and the expression of Notch downstream effectors hairy‐related transcription factors (HRT). Similarly, TGFβ1 treatment of HASMC induced SM actin, calponin1, and smooth muscle protein 22‐α (SM22α) in a dose and time‐dependent manner. HRT proteins, which antagonize Notch activity, also suppressed the TGFβ1‐induced increase in SMC markers, suggesting a general mechanism of inhibition. We found that Notch and TGFβ1 cooperatively activate SMC marker transcripts and protein through parallel signaling axes. Moreover, the combination of Notch activation and TGFβ1 treatment led to synergistic activation of a TGFβ1 responsive SM specific gene promoter by the interaction of CBF1 and pSmad2/3. Thus, Notch and TGFβ1 coordinately induce a molecular and functional contractile phenotype by co‐regulation of Smad activity at SMC promoters.Grant Funding Source: NIH NCI