bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fibrocytes are Increased in the Medial Layer of the Aorta from Spontaneously Hypertensive Rats
Authors: McKenzie Jaine , Arishe Olufunke , Ogbi Safia , Quinones Patricia Martinez , Klee Nicole , Khodadadi Hesam , Komic Amel , Baban Babak , Webb Clinton 
Published: June 2021

BackgroundChronic hypertension causes a state of inflammation and leads to vascular remodeling. Vascular remodeling involves alterations in vascular smooth muscle cells, endothelium, and extracellular matrix. Collagen deposition is increased in conductance and resistance vessels of hypertensive animals.Fibrocytes are bone marrow‐derived cells found in the circulation that migrate toward injured tissue. At the injured site, fibrocytes contribute to healing by serving as antigen presenting cells and secrete cytokines such as IL‐6 and IL‐8 to recruit T cells. Fibrocytes also lay down extracellular matrix such as collagen, and its activation is implicated in many fibrotic diseases including cardiac fibrosis. Studies have shown that patients with hypertensive heart disease have increased number of circulating fibrocytes and that hearts of hypertensive patients have increased collagen levels. The role of fibrocytes in vascular remodeling in hypertension have not been investigated.HypothesisThis study tests the hypothesis that fibrocytes are increased in hypertension and play a role in vascular remodeling.MethodsMale spontaneously hypertensive rats (SHR) and Wistar rats 13–16 weeks old were used in this study. Flow cytometry was used to determine the percentage of fibrocytes (CD34+/CD45+/CollagenI+) in the peripheral blood, aorta, mesenteric resistance arteries (MRA), and pudendal arteries. Wire myograph was used to evaluate the differences in vascular function in response to phenylephrine (PE), norepinephrine (NE), acetylcholine (ACh), and sodium nitroprusside (SNP) between SHR and Wistar. Immunohistochemistry was used to detect fibrocytes (CD34+/CD45+/Collagen I+) within the vascular walls of aorta, mesenteric, and pudendal arteries. Statistical analysis performed using nonlinear regression, two‐tailed unpaired t‐test, and two‐way ANOVA.ResultsFlow cytometry did not show a difference between the percentage of fibrocytes in SHR compared to Wistar. Wire myography demonstrated differences between the two groups in aortic contraction to PE (p<0.0001) and NE (p<0.0001), aortic relaxation to ACh (p<0.0001) and SNP (p<0.0001), MRA relaxation to ACh (p<0.0001), and pudendal artery relaxation to SNP (p<0.0001). Immunohistochemistry showed increased number of fibrocytes in the media layer of the SHR aorta (Figure 1) compared to Wistar (Figure 2).ConclusionsThe number of fibrocytes are increased in the media layer in the aorta in SHR compared to Wistar. The increased number of fibrocytes may contribute to increased collagen deposition leading to decreased vascular compliance in hypertensive animals.Support or Funding InformationNIH P01 HL‐134604This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Group versus Individual Exercise Differentially Affects Stress Hormone Release in Zebrafish (Danio rerio)
Authors: Jones Alexis , Garcia Emily 
Published: June 2021

Zebrafish (Danio rerio) are a small, tropical freshwater fish native to Southeast Asia. They are advantageous to the study of behavior and physiology due to their high physiological and genomic homology to mammals, external fertilization, rapid development, ease of experimental manipulations, and cost‐ and space‐effectiveness. It is well known that exercise is beneficial, but it is becoming increasingly important to understand the psychological and physiological consequences (both positive and negative) to individuals who engage in exercise. The purpose of this experiment was to determine whether cortisol release was affected by group versus individual exercise in zebrafish. Adult, wild‐type male and female zebrafish housed in a community aquarium were exercised in a swim tunnel at a moderate intensity for 10–20 minutes either individually or in small groups (4–5). Control fish were placed in the swim tunnel but it was not turned on. Immediately following each exercise bout, fish were placed in small containers of water to collect cortisol secreted from their gills. Fish that were exercised in a group had lower cortisol levels compared to fish that exercised individually. Fish that were kept in a group, whether exercised or not, secreted less cortisol during the subsequent sampling period. Exercising alone seems to cause the greatest stress response in zebrafish; fish that were exercised individually secreted the greatest amount of cortisol compared to other groups.Support or Funding InformationResearch in this abstract was supported by the National Institute of General Medical Sciences of the National Institutes of Health under award number P20GM103447. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Binge but Not Moderate Drinking Impairs Microvascular Flow Induced Dilation Following High Pressure in Young Adults
Authors: Hwang Chueh‐Lung , Bian Jing‐Tan , Thur Laurel A , Peters Tara A , Piano Mariann R , Phillips Shane A 
Published: June 2021

Binge drinking or heavy‐episodic drinking is an emerging cardiovascular risk factor and is prevalent among young adults. On the other hand, moderate drinking may also increase cardiovascular risk. We previously demonstrated that flow‐induced dilation (FID) is reduced in young adult binge drinkers compared to abstainers. However, little is known about alteration associated with alcohol use in the vascular response to environmental stress (e.g. high pressure) or vascular function in moderate drinkers. Therefore, we sought to examine FID following high pressure in binge drinkers, moderate drinkers, and abstainers. In addition, we used tetrahydrobiopterin (BH4) to investigate the possible underlying mechanism. We isolated arterioles from gluteal subcutaneous adipose biopsies from 33 young adults (binge drinkers: n=12, moderate drinkers: n=11, and abstainers: n=10; age: 24±1 yrs and body mass index: 23.6±0.4 kg/m2; mean±SE). Arterioles were cannulated and pressurized (60 cmH2O) in an organ perfusion chamber. Lumen diameters were measured before and during responses to flow (pressure gradients of Δ10‐Δ100 cmH2O) prior to and following 1‐hour high intraluminal pressure (150 cmH2O) in the presence or absence of BH4 (10−5 M). Prior to high pressure, we found that moderate drinkers had similar FID across all pressure gradients as abstainers (P>0.1). At Δ100 cmH2O pressure gradient, both moderate drinkers and abstainers had higher % vasodilation than binge drinkers (13% higher, P=0.0047 and 20% higher, P<0.0005 respectively). This impairment in binge drinkers was restored by BH4 (+12%, P=0.02 vs. absence of BH4 and P>0.06 vs. moderate drinkers and abstainers). Following high pressure, FID was reduced only in binge drinkers (3–17% lower, P=0.005 vs. prior to high pressure) while the vasodilatory response to flow was maintained in moderate drinkers and abstainers (P>0.4 vs. prior to high pressure). BH4 ameliorated the impaired FID following high pressure across all pressure gradients in binge drinkers (+4–26%, P<0.05 vs. absence of BH4). In conclusion, arterioles from young adults who abstain or who drink moderately show maintained FID following exposure to elevated vascular pressure. The impaired FID associated with binge drinking can be further reduced by high pressure and reversed by treatment with BH4, suggesting endothelial nitric oxide synthase uncoupling in endothelial dysfunction induced by high pressure in binge drinkers.Support or Funding InformationNIH R01 HL095701 and R21 AA024535This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Greater α1‐ and α2‐Adrenergic Mediated Vasoconstriction in Contracting Skeletal Muscle of Type 2 Diabetic Humans
Authors: Bock Josh , Hughes William , Ueda Kenichi , Feider Andrew , Hanada Satoshi , Kruse Nicholas , Iwamoto Erika , Casey Darren 
Published: June 2021

Type 2 diabetics (T2D) have diminished exercise capacity (VO2max), an independent risk factor for cardiovascular disease. Inadequate blood flow during exercise largely contributes to the reduced VO2max characteristic of T2D. Offsetting sympathetic‐mediated, α‐adrenergic vasoconstriction in contracting skeletal muscle (i.e., functional sympatholysis) is a key regulatory mechanism matching O2 supply (blood flow) with demand (metabolism). Thus, we studied if functional sympatholysis was impaired in 18 T2D (13M/5F) versus 15 control subjects (10M/5F) using intra‐arterial infusions of phenylephrine (PE, α1‐agonist) and dexmedetomidine (DEX, α2‐agonist) at rest, as well as during handgrip exercise. Handgrip exercise trials lasted for 6min at a workload of 20% maximum grip strength. Steady‐state (SS) blood flow was achieved during the first 3min with either PE or DEX infused during the latter 3min. Forearm blood flow (FBF, ml/min) was calculated using brachial artery diameter and blood velocity measured via Doppler ultrasound. Forearm vascular conductance (FVC, ml/min/100mmHg) was calculated using FBF and mean arterial pressure (MAP, measured intra‐arterially). Both FBF and FVC were calculated from data averaged over the final 30sec of rest and SS exercise (before and during infusions). Functional sympatholysis for both PE and DEX trials (resting and exercise) was quantified as: ((SS FVCwith drug – SS FVCpre‐drug)/SS FVCpre‐drug)x100%. T2D and control subjects were of similar age (60±9 vs. 60±9years, p=0.87) and body mass index (30.9±5.5 vs. 29.5±4.6kg/m2, p=0.42); however, VO2max was lower in T2D compared to controls (20.7±5.9 vs. 27.7±8.5ml/kg/min, respectively, p<0.01). No differences in resting FBF, FVC, α1‐ or α2‐mediated vasoconstriction were observed between T2D and controls (p>0.05 for all). In response to handgrip exercise, T2D had 20% lower FBF (166±71 vs. 199±66ml/min, p=0.09) and 24% lower FVC (142±59 vs. 177±52ml/min/100mmHg, p<0.05) compared to controls, respectively. Of particular interest, α1‐ (−16.6±5.9 vs. −10.9±4.3%, p<0.01) and α2‐mediated (−23.8±6.6 vs. 19.5±7.0%, p<0.05) vasoconstriction during handgrip exercise was greater in T2D compared to controls. These data suggest impaired functional sympatholysis may contribute to the diminished exercise capacity of T2D and therefore, could increase their risk of developing cardiovascular disease.Support or Funding InformationAmerican Diabetes Association 1‐16‐ICTS‐015This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Influence of Diisopropyl fluorophosphate, an irreversible cholinesterase inhibitor, on metabolic and inflammatory parameters, cardiac function, autonomic modulation, and angiotensin 1–7 receptor
Authors: Stoyell‐Conti Filipe Fernandes , Machi Jacqueline F , Schmidt Rodrigo , Puthentharayil Joseph , Benny Alin , Rola Darshan , Lee Matthew , Muthuraj Muthunivas , Speth Robert C , Morris Mariana 
Published: June 2021

Nowadays, an estimate of 25–32% of approximately 700,000 Gulf War veterans affected by the Gulf War illness (GWI) still experience symptoms associated with their deployment. It is important to emphasize that GWI is an archetypal, medically unexplained, chronic condition. Musculoskeletal pain, cognitive dysfunction, unexplained fatigue, exercise intolerance, chronic diarrhea, rashes, sleep disorders, and respiratory problems are some of the symptoms observed in Gulf War veterans affected by GWI. Understanding the mechanisms involved in GWI is important to provide a better assistance/treatment to this population. In this study, we used mice to verify the influence of Diisopropyl fluorophosphate (DFP), an irreversible cholinesterase inhibitor used to mimic the effects of sarin gas used during the Gulf War, on metabolic and inflammatory parameters, cardiac function (ECHO), autonomic modulation (spectral analysis) and angiotensin 1–7 receptor (Radioligand Binding Assay) in liver. The animals exposed to DFP showed lower levels of glucose (−8%), triglycerides (−23%) and IL‐10 (−32%), lower parasympathetic modulation (−33%), which led to a higher sympathovagal balance. They showed a lower ejection fraction (−13%) and higher myocardial performance index (30%), characterizing a cardiac dysfunction. In addition, they showed higher Bmax for 125/127I‐Angiotensin 1–7 binding assay, which represents a higher number of receptors (28%). Our results show that exposure to DFP leads to alterations on metabolic and inflammatory parameters, cardiac function, autonomic modulation, and renin‐angiotensin‐aldosterone system, which helps us to understand, at least in part, the mechanisms involved in GWI. Further studies are needed to elucidate the whole mechanisms behind GWI.Support or Funding InformationW81XWH‐13‐2‐0085 Morris (PI); Cardiovascular Neuroscience Research Fund 337667 Speth (PI)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Sensory Nerve‐Mediated and Nitric Oxide‐Dependent Vasodilation Is Reduced in Non‐Hispanic Blacks Compared to Non‐Hispanic Whites
Authors: Walker Demetria , Hollowed Casey , Miller James , Otis Jeffrey , Hayat Matthew , Quyyumi Arshed , Wong Brett 
Published: June 2021

Reduced microvascular function is recognized in healthy non‐Hispanic Blacks compared to non‐Hispanic Whites, but it is unclear whether sensory nerve function is altered in non‐Hispanic Blacks. Local heating of the skin allows for the simultaneous assessment of both sensory nerve‐mediated and nitric oxide (NO)‐dependent vasodilation. The purpose of this study was to test the hypothesis that the magnitude of cutaneous sensory nerve‐mediated and microvascular endothelial‐dependent vasodilation is reduced in non‐Hispanic Blacks compared to non‐Hispanic Whites. Six healthy participants who self‐identified as non‐Hispanic Black (n=3) or non‐Hispanic White (n=3) were instrumented with two microdialysis fibers on the forearm: 1) lactated Ringer's (control) and 2) topical anesthetic (5% lidocaine) to inhibit sensory nerve function. A rapid local heating protocol was conducted at each microdialysis site where the temperature of the skin was heated from 33°C to 39°C at a rate of 1°C/sec. Skin blood flow was continuously monitored at each site with laser‐Doppler flow (LDF) probes. At the plateau of skin blood flow, 20 mM L‐NAME was perfused at each site to inhibit NO synthase in order to calculate %NO‐dependent vasodilation. Following L‐NAME infusion, maximal skin blood flow was reached by infusing each site with 54 mM sodium nitroprusside and heating the skin to 43°C. Cutaneous vascular conductance (CVC) was calculated (LDF/MAP) and standardized to maximal blood flow (%CVCmax). Data shown are mean ± SD. At control sites, the initial peak (33 ± 9 %CVCmax) and plateau (52 ± 9 %CVCmax) in non‐Hispanic Blacks were reduced compared to non‐Hispanic Whites (53 ± 8 % and 67 ± 10 %CVCmax; P < 0.05 for all conditions). At sites treated with anesthetic, the initial peak was unaltered in non‐Hispanic Blacks (26 ± 10 %CVCmax) but was significantly reduced in non‐Hispanic Whites (23 ± 13 %CVCmax). Anesthetic did not affect the plateau in either non‐Hispanic Blacks (56 ± 5 %CVCmax) or non‐Hispanic Whites (62 ± 4 %CVCmax). Calculated %NO‐dependent vasodilation was reduced in non‐Hispanic Blacks (51 ± 6 %NO) compared to non‐Hispanic Whites (67 ± 8 %NO). These data indicate that sensory nerve function, microvascular function, and NO‐dependent vasodilation are all decreased in non‐Hispanic Blacks in comparison to non‐Hispanic Whites.Support or Funding InformationNIH R01HL141205This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Loss of Muscle IGF‐I Production Delays Functional Recovery of Skeletal Muscle Following Disuse
Authors: Spradlin Ray Allen , Vassilakos Georgios , Matheny Michael , Jones Nathan C , Goldman Jessica , Lei Hanqin , Barton Elisabeth R 
Published: June 2021

PurposeInsulin‐like growth factor‐I (IGF‐I) is an important coordinator of muscle growth, repair, and functional capacity while disuse‐induced skeletal muscle atrophy is a consequence of many diseases and injuries that require prolonged rest. It is known that a lack of muscle activity results in loss of skeletal muscle mass and force generating capacity but it is unclear if locally produced IGF‐I is necessary for recovery from disuse.MethodsMice with muscle‐specific inducible deletion of IGF‐I (MID) and age‐matched controls (CON) underwent hindlimb suspension (HLS) and reloading. Deletion was achieved by the addition of 2mg/mL doxycycline hyclate with 5% sucrose to the mice's drinking water prior to suspension and maintained throughout the course of the experiment. Mice were either left non‐suspended (NS) or suspended for 7 days (SUS) and reloaded for 3 days (Re3), 7 days (Re7), and 14 days (Re14). EDL and soleus muscle function were assessed at each timepoint and tissues were harvested to assess extent of Igf1 deletion, as well as changes in mass, gene expression (qPCR), and IGF‐I content (ELISA). All groups were compared to NS CON mice.ResultsThroughout the duration of the experiment, neither MID or CON mice's body weight changed significantly. During suspension, CON mice exhibited a 20% reduction in soleus mass and no changes for the EDL when normalized to body weight. No normalized mass changes in either muscle were seen in the MID group following suspension. Force generating capacity in CON mice was unaffected by suspension/reloading, while MID mice had a 20 and 23% reduction in specific force for the EDL and soleus, respectively, in SUS and Re7 mice. CON mice showed a reduction of muscle IGF‐I content upon suspension, a marked increase at Re7, and a return to baseline values by Re14. MID mice showed a trend for lower initial IGF‐I levels and remained reduced throughout the course of the experiment. Fiber type distribution and cross‐sectional area did not seem to be significantly affected by Igf1 deletion or suspension/reloading. Fbxo40, Musa1, and Smart expression were unchanged while endogenous Igf1 expression was significantly lower at Re7 in the MID mice compared to CON.ConclusionsWe conclude that a local source of IGF‐I is necessary for muscle recovery from disuse.Support or Funding InformationThis study was supported in part by U54 AR052646This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Identification and Characterization of Protein Phosphatase Methylesterase 1 (Ppme1) in Skeletal Muscle
Authors: Labuzan Sydney , Waddell David 
Published: June 2021

Skeletal muscle atrophy results from a range of physiological conditions, including immobilization, denervation, glucocorticoid treatment, cancer, and aging. To provide a better understanding of the pathway of skeletal muscle atrophy, a previous study conducted a microarray analysis of muscle from mice undergoing neurogenic atrophy in response to denervation as well as dexamethasone exposure. The data generated from this microarray identified a suite of several hundred predicted genes that displayed differential expression under conditions of muscle wasting, including protein phosphatase methylesterase‐1 (Ppme1). The Ppme1 gene was observed to be transcriptionally upregulated in response to neurogenic skeletal muscle atrophy (i.e. denervation). To confirm that Ppme1 is expressed in muscle, qPCR was performed using RNA isolated from cultured muscle cells at different stages of proliferation and differentiation and expression was found to be relatively constant in both proliferating and differentiated cells. In addition, Ppme1 protein levels were analyzed by Western blot analysis and found to be expressed at a constant level at different time points throughout muscle cell proliferation and differentiation. Additionally, the cDNA of Ppme1 was fused in frame with GFP and subcellular localization was analyzed by confocal fluorescent microscopy in proliferating myoblasts. To assess the transcriptional activity of the Ppme1 gene, fragments of the promoter were cloned, fused to a reporter gene, transfected into C2C12 cells, and found to be highly transcriptionally active. Interestingly, the Ppme1 reporter gene constructs were not significantly affected by ectopic expression of myogenic regulatory facts such as MyoD1 and myogenin. Finally, mouse myoblast cells treated with an inhibitor of Ppme1 displayed reduced AP‐1 reporter activity as well as delayed muscle cell differentiation. The results presented here help contribute new insights into the molecular mechanisms of muscle atrophy and may provide a better understanding of the genome‐wide transcriptional changes and cellular events that occur during skeletal muscle wasting.Support or Funding InformationThe work was support by University of North Florida Transformational Learning Opportunity grants and a University of North Florida Foundation Board Grant to D.W.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.