bluuebunny/crossref_metadata_2025 huggingface dataset:
Resistive exercise with or without super‐imposed whole‐body vibration acutely induces bone resorption
Authors: Lau Patrick , Beijer Åsa , Rosenberger André , Zange Jochen , Rittweger Jörn
Published: June 2021

Background

Exercise is one of the well‐known constituents to improve bone mass and to retain bone strength. Only few studies have reached the effects of resistive exercise on sclerostin levels, a protein that is thought to play a key role in orchestrating bone's mechanical adaptation. Sclerostin is produced and released by osteocytes and acts as an inhibitor of bone formation through inhibition of the Wnt/β‐catenin‐signaling pathway. The objective of this study was to evaluate acute and long‐term effects of exercise on bone biochemical marker expression. More specifically, we aimed to understand differences in the responses to resistance exercise with or without whole‐body vibration.

Methods

A six week training intervention was performed including 26 healthy males (26 years, SD=4) in in a randomized parallel design. Performing either resistive exercise (RE, n=13) or resistive vibration exercise (RVE, n=13) training, with weekly increasing vibration frequencies 20–40 Hz. Serum samples were collected both at the initial and final exercise session. Changes in carboxy‐terminal cross‐linked telopeptide of type I collagen (sCTX‐I), as a marker of bone resorption, and of procollagen type I amino terminal propeptide (P1NP) as a specific marker of bone formation as well as serum sclerostin concentrations were measured via ELISA (sCTX‐I and sclerostin) or RIA (P1NP) measurements.

Results

Serum markers of sCTX‐I decreased by 15% within the first minutes following either training intervention, both regarding the initial and final training session. Subsequently, levels of sCTX‐I returned back to pre‐bout baseline after RE (time effect: P<0.001), and they depicted an overshoot by 18% after 75 min. Serum levels of P1NP depicted an acute increase by 15% to exercise (P<0.001). P1NP levels were non‐substantially increased in RE at the end of the 6 week intervention (P<0.001), but decreased by 10% in RVE, as compared to baseline (P< 0.001). Pre‐bout levels of sclerostin were marginally lowered at the end of the 6 week training phase. After the exercise bouts, sclerostin levels increased within the first minutes both RE and RVE (time effect: P<0.001). Notably, sclerostin responses to the initial exercise bouts differed significantly between RE and RVE P=0.029.

Conclusion

The present findings suggest that in young healthy adults both conditions RE and RVE elicited an acute exercise‐induced bone resorption without any acute change in bone formation. Results are compatible with the idea that this response was mediated by sclerostin.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
CaMKKβ regulates store‐operated calcium entry (SOCE) through controlling the expression of STIM1 in endothelial cells
Authors: Regmi Sushil C. , Soni Dheeraj , Wang DongMei , Tiruppathi Chinnaswamy
Published: June 2021

Here, we provide evidence for the first time that CaMKKβ regulates store‐operated Ca2+ entry (SOCE) through controlling the transcription of stromal interaction molecule 1 (STIM1), a crucial activator of SOCE in endothelial cells (ECs). Surprisingly, we observed drastically reduced expression of both mRNA and protein for STIM1 in lung tissue and lung ECs of CaMKKβ knockout (CaMKKβ−/−) mice compared with wild type. Interestingly, expression of STIM2, TRPC1, TRPC4, Orai1, Orai2, and Orai3 was unaltered in CaMKKβ−/− mice. Knockdown of CaMKKβ in human lung microvascular endothelial cells (HLMVECs) also suppressed STIM1 expression. Importantly, we observed complete loss of SOCE in LECs of CaMKKβ−/− mice compared to the wild type mice. Since CaMKKβ may regulate gene expression through epigenetic mechanism, we analyzed STIM1 gene sequence and observed the presence of methylation‐prone CpG sites in 5′‐regulatory of both human and mouse STIM1 genes. DNA methylation analysis revealed hypermethylation of ST1M1 promoter in CaMKKβ−/− mice compared to WT mice. Interestingly, i.p injection of 5‐azacytidine, a methyl transferase inhibitor restored STIM1 expression in lungs of CaMKKβ−/− mice. In addition, liposome‐mediated in vivo delivery of WT‐CaMKKβ but not by K193A‐CaMKKβ plasmid restored STIM1 expression in lung ECs of CaMKKβ−/− mice. These findings demonstrate the prerequisite role of CaMKKβ in regulating STIM1 transcription through epigenetic mechanism in endothelial cells.

Support or Funding Information

National Institute of Health Grants R01 HL‐128359 and R01 GM‐117028

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
INCREASED PLASMA IL‐1 CONCENTRATIONS IN POLYCYSTIC OVARYINDUCED RATS
Authors: Sanches Reginaldo Batistela Pietro , Alves Eduardo Donato , Benevenuto Luiz Guilherme Décore , Montrezor Luís Henrique
Published: June 2021

Polycystic ovary syndrome (PCOS) is a clinical disorder that affects up to 15% of women of reproductive age, and is the most common endocrine disorder among pre‐menopausal women. PCOS is characterized by impairment of ovulation, reduced fertility, and imbalance of reproductive hormones. In addition, women with PCOS often exhibit obesity, metabolic syndrome, hyperinsulinemia, insulin resistance, and dyslipidemia. Adipose tissue secretes hormones that contribute to processes that regulate metabolism, inflammatory responses, immunity, and reproduction. In obesity, body fat deposits are hypertrophied, stimulated by androgens that influence the expression of enzymes and proteins involved in lipid and carbohydrate metabolism, oxidative stress, and differentiation of pre‐adipocytes into mature adipocytes. A consequence of hypertrophy and adipose hyperplasia is the expression of pro‐inflammatory cytokines. The goal of this study was to analyze the plasma variations of interleukin‐1 (IL‐1) in rats induced to polycystic ovary (PCO). Ten female adult Wistar rats weighing 200–340 g were divided into control (n = 5) and PCO (n = 5) groups. PCO was induced in the rats by single injection of estradiol valerate (EV) (2 mg/kg/bw, i.m.). The two groups of rats were then evaluated after 30 days. The results were reported as means ± SEM. Statistically significant differences among the means for the treatment groups were identified using p<0.05. This study was approved by the local Animal Care and Use Committee (CEUA–UNIARA, protocol n° 031/16). The results showed that the body mass of the control group (344 ± 13.56 g) was higher than that of the PCO group (306.4 ± 32.35 g). The ovary mass of the control group (0.072 ± 0.004 g) was higher than for the PCO group (0.048 ± 0.005 g), and the gonadal somatic index of the control group (0.0257 ± 0.006) was also higher than for the PCO group (0.0166 ± 0.008). Finally, the plasma IL‐1 concentration of the PCO group (55.68 ± 13.15 pg/mL) was higher than for the control group (21.62 ± 5.78 pg/mL). The results were indicative of metabolic and inflammatory changes in the rats 30 days after the PCO induction.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Oral NaHCO3 activates the splenic anti‐inflammatory pathway; evidence vagal efferent signals are transmitted to the spleen via a neuronal like function of mesothelial cells.
Authors: O'Connor Paul M. , Marshall Brendan , Baban Babak , Ocasio Hiram , Wilson Katie , Sun Jingping , Ray Sarah
Published: June 2021

We tested the hypothesis that ‘Oral NaHCO3 intake stimulates splenic anti‐inflammatory pathways. Following oral NaHCO3 loading, macrophage polarization was shifted from predominantly M1 (inflammatory) to M2 (regulatory) phenotypes in the spleen and kidneys of rats, and in the blood of human subjects. Surprisingly, we found that gentle manipulation to visualize the spleen at midline during surgical laparotomy (sham splenectomy) was sufficient to abolish the response and resulted in hypertrophy/hyperplasia of the capsular mesothelial cells. Thin collagenous connections lined by mesothelial cells were found to connect to the capsular mesothelium. Mesothelial cells in these connections stained positive for the pan‐neuronal marker PGP9.5 and acetylcholine esterase and contained many ultrastructural elements which visually resembled neuronal structures, including synaptic ribbons (the presence of which was confirmed by immunohistochemistry). Both disruption of these fragile connections or transection of the vagal nerves below the diaphragm, resulted in loss of capsular mesothelial acetylcholine esterase staining and a significant reduction in splenic mass, which was not additive. Our data indicate that oral NaHCO3 activates the cholinergic anti‐inflammatory pathway and provides evidence that the signals that mediate this response are transmitted to the spleen via a novel neuronal like function of mesothelial cells.

Support or Funding Information

This work was supported by grants to Paul O'Connor (NIH DK099548 and 1P01HL134604)

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Fluorescent Based Tracing of Sensory Nerve Subtypes in Vagal Ganglia and Lung
Authors: Kim Seol‐Hee , Taylor‐Clark Thomas
Published: June 2021

Cell bodies of airway afferent nerves originate from vagal ganglia and vagal afferent nerves project to the respiratory tract. The inputs from these nerves converge at the brainstem to regulate respiratory reflexes. These vagal afferent nerves can be classified into various subtypes based on the origins of cell bodies in vagal ganglia, conduction velocity, size and stimuli required for activation. The polymodal nature of vagal afferent nerves complicates the study of respiratory reflexes. Transient receptor potential vanilloid 1 (TRPV1) is one of the ion channels expressed in bronchopulmonary C‐fibers. Tachykinin 1 (Tac1) encodes for a neuropeptide, Substance P, which is released from sensory nerve terminals in jugular originated afferent nerves. 5HT3 is expressed in nodose originated nociceptive C‐fibers. In the present study, we focused on defining afferent nerves subtypes in vagal ganglia based on ion channel/receptor expression as well as innervation into respiratory tract using a transgenic mouse model.

The Cre‐LoxP reporter system was used to target specific populations of afferent nerve subtypes and to control red fluorescent protein (tdTomato) expression. Trpv1‐Cre, Tac1‐Cre and 5ht3‐Cre strains were bred with Floxed Ai9 ROSA tdTomato; thus, expressing red fluorescent in Trpv1, Tac1 and 5ht3 positive neurons. Mice (6 to 8‐week‐old) were euthanized and tissues were collected. Lungs were inflated with 3 % low‐melting agarose solution and sectioned at 100 μm using a vibratome. Immunohistochemistry was done using anti‐E‐Cadherin and anti‐dsRed antibodies. Vagal ganglia were dissected and cryo‐sectioned at 20 μm. Immunohistochemistry was done using anti‐Trpv1 antibody to compare with native tdTomato expression. Images were taken using Olympus FV1200 confocal microscope.

Native tdTomato expression for Trpv1 positive afferent nerves were seen in both jugular and nodose ganglia. tdTomato tagged for Tac1 positive afferent nerves were mostly expressed in jugular and some in nodose ganglia, while 5ht3 positive afferent nerves were exclusively in nodose ganglia. The native tdTomato expression of 5ht3 positive afferent nerves did not completely overlap with anti‐TRPV1 staining. We further visualized the nerve endings that projected from vagal ganglia into lung and the tdTomato expression patterns of the nerve endings were different depending on strains. With Trpv1 strain, nerve endings spread out in all the lobes and those nerve endings resided in the epithelial layer, mainly around the bronchi.

Overall, we were able to identify the distinct locations of cell bodies in vagal ganglia and nerve endings in lung of various subsets of airway afferent nerves using Cre‐LoxP reporter system. This information may be valuable to investigate the highly complicated mechanism of respiratory reflexes.

Support or Funding Information

NIH Common Fund SPARC OT2

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
One Cause of Sensorineural Hearing Loss for Meniere's disease, Otosyphilis, and Enlarged Vestibular Aqueduct Syndrome from MR findings
Authors: Tanioka Hisaya
Published: June 2021

Objectives/Hypothesis

To evaluate conditions of the endolymphatic duct and sac of normal subjects, Meniere's disease (MD), late congenital otosyphilis, and enlarged vestibular aqueduct syndrome (EVAS) from high‐resolution MR imaging. Although these diseases present similar clinical symptoms, the basic etiology is veiled. Comparing their pathological evidence with these MR features results in one hypothesis of the causes of MD, late congenital otosyphilis, and EVAS.

Study Design

Retrospective study

Materials and Method

10 normal ears, 10 unilateral MD, 1 unilateral EVAS, and 1 late congenital Otosyphilis underwent 1.5T MR scanner. The scan sequences were as follows; SE (T1‐W, Proton Density, and T2‐W), FISP (T2‐W) and FLASH (Proton Density).

Results

Although the normal endolymphatic duct and sac were depicted relatively low signal in all sequences, the rugose portion of the sac was imaged as a low signal constriction. In MD, there were two patterns imaging. One lacked imaging of the endolymphatic duct. In the other, there was stenosis in the part of the rugose portion. In EVAS, the endolymphatic duct and sac showed enlargement with high signal fluid on T2‐WI. In the late congenital syphilis, the enlarged endolymphatic duct and sac compounded with the soft tissue irregular intensified substances were depicted.

Conclusions

Under normal conditions, the normal endolymphatic duct and sac are depicted in low signal intensity by all MR imaging sequences. That is, if a certain part will be depicted as a high signal, the lesion will be considered as an abnormality. Hence, in EVAS, this fact indicates that the high signal endolymphatic and duct in T2‐WI are abnormal status. This condition will be caused by stagnation of the endolymph. The stagnation is the inhibition of the endolymphatic flow itself. The symptoms of otosyphilis will be caused that the endolymphatic duct and sac are occluded by the microgummata and fibrotic substances, and the endolymphatic flow is obstructed. However, In MD, the causes are complicated in this study. There are two possible obstructive lesions in the endolymphatic duct and sac. One seems to be deeper than the sinus in the proximal part of the endolymphatic duct, because the endolymphatic duct cannot be depicted in MR imaging. The other will be at the rugose portion of the sac. In the later pattern, the endolymphatic duct may be imaged at parts with high intensified spot on T2‐WI. Any patient with unexplained sudden deafness should be screened for syphilis.

Support or Funding Information

Conflict of Interest

The author of this manuscript declares no relationship with any companies, whose products or services may be related the subject matter of the articlcle. Funding: The author states that this work has not received any fundings.
Carbonic Anhydrase Inhibition: Effect on Rat Hearts In Vitro With and Without pH Perturbations
Authors: Wasinger Nicholas A. , Geisbuhler Timothy P. , Brechue William F.
Published: June 2021

Myocardial force generation is modulated by stretch‐induced mechanisms. The Starling effect relates to increased force following stretch due to venous return. The Anrep effect is a change in contractility with stretch secondary to increased afterload. Both mechanisms are related to intracellular Ca2+ dynamics. Carbonic anhydrase (CA) catalyzes the reversible hydration of carbon dioxide (CO2) which is involved in cellular acid‐base balance. In skeletal muscle in vitro, inhibition of CA leads to increased fatigue due to altered Ca2+ handling at the sarcoplasmic reticulum. Our purpose was to investigate the role of CA in stretch‐induced change in myocardial force generation.

Methods

Hearts from Sprague‐Dawley rats were perfused in the working Langendorff style with Krebs‐Henseleit buffer [pH +/− 7.35 or 6.20, supplemented with 0.2 to 0.8% serum albumin (BSA)] and allowed to equilibrate 5 min under baseline preload (10 mmHg) and afterload (55 mmHg) conditions. Performance was examined at preloads of 10, 15, and 20 mmHg and constant afterload (55 mmHg); preload was then returned to 10 mmHg, and performance examined at afterloads of 55, 60, and 65 mmHg with constant preload (10 mmHg). Ethoxzolamide (Eth, 0.1 μM) or vehicle (water) was added to the perfusing buffer and the preload/afterload protocol repeated after 5 min equilibration with treatment. Systolic and diastolic pressure, heart rate, and dP/dt were monitored during the protocol. Performance was evaluated for individual parameters as a ratio of (value post‐addition)/(value pre‐addition) (hereafter called Ppost/Ppre).

Results

Colloids in the perfusing medium preserve cardiac performance by preventing tissue edema. Cardiac performance (that is, the ability of the heart to maintain output and pressure) was best preserved over 40 min using BSA=0.8% (w/v). Dropping the pH to 6.2 from 7.35 increased Ppost/Ppre with regard to mean systolic pressure [1.04 ± 0.14 at 6.2 vs 0.47 ± 0.48 at 7.35 (p <0.05)], decreased Ppost/Ppre for peak systolic pressure [0.97 ± 0.02 at 6.2 vs 1.05 ± 0.03 at 7.35 (p <0.05)], and decreased Ppost/Ppre for minimum diastolic pressure [1.07 ± 0.01 at 6.2 vs 1.18 ± 0.06 at 7.35 (p <0.05)]. Addition of Eth decreased Ppost/Ppre for peak systolic pressure [1.00 ± 0.02 at 7.35 with Eth vs 0.89 ± 0.05 at 7.35 without Eth (p <0.05)] and increased Ppost/Ppre for minimum diastolic pressure [1.03 ± 0.05 at 7.35 with Eth vs 1.18 ± 0.06 at 7.35 without Eth (p <0.05)] at pH=7.35. Addition of Eth neither increased nor decreased Ppost/Ppre for any performance parameter examined at pH=6.20.

Conclusion

CA inhibition may lead to correction of function disrupted by pH perturbation.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Role of PI3‐kinase in Angiotensin II‐induced Cardiac Hypertrophy: Shift from Class III to Class I
Authors: Zhong Tiecheng , Guo Lirong , O'Rourke Stephen T. , Sun Chengwen
Published: June 2021

Cardiac hypertrophy is initially an adaptive response to increased hemodynamic workload or defective contractile machinery; however, in the long‐term, it contributes to heart failure and sudden cardiac death. The extracellular regulatory factors and intracellular signaling pathways involved are not fully clear. Here, we studied the chronic effect of Ang II infusion on cardiac hypertrophy and fibrosis, and evaluated the role of class I PI3‐kinase in these actions of Ang II using lentiviral vector‐mediated expression of a dominant negative form of Class I PI3‐kinase subunit p85α in the heart of rats. Subcutaneous 4‐week infusion of Ang II induced severe cardiac hypertrophy and perivascular fibrosis in the heart. Cardiac transduction of Lv‐DNp85 abolished Ang II‐induced phosphorylation of Akt in the heart, as well as Ang II‐induced cardiac hypertrophy and perivascular fibrosis. Next, we examined intracellular mechanisms underlying Ang II‐induced cardiac hypertrophy in cultured cardiomyocytes. It is well known that mitochondrial oxidative stress mediates Ang II‐induced cardiac hypertrophy and the major source of reactive oxygen species (ROS), damaged mitochondria, is cleared by autophagy (also called mitophagy) in cardiac myocytes. Treatment of cardiomyocytes with Ang II (10−9 to 10−5 M) significantly increased autophagy with two phases (increases at low doses, decreases at high doses, peaked at 10−7 M). Ang II (10−6 M)‐induced increases in autophagy were significantly potentiated by PI3‐kinase Class I inhibitor, LY294002 (1 μM) and dramatically attenuated by 3‐Methyladenine (3‐MA, 1 μM), a PI3‐kinase Class III inhibitor. Ang II‐induced mitochondrial ROS production, measured using MitoSOX, was attenuated by LY294002 and potentiated by 3‐MA significantly. PI3‐kinases activity were measured using ELISA in cardiomyocytes, demonstrating that Ang II (10−6 M, i.e. high dose) significantly increased the activity of both Class I and Class III PI3‐kinases; however, Ang II (10−9 M, i.e. low dose) selectively elevated PI3‐kinase Class III activity. Together these data suggest that Ang II could have dual effects in the heart: 1) a protective arm to prevent ROS over‐generation in physiological cardiac hypertrophy, which is mediated by a Class III PI3‐kinase/autophagy‐dependent pathway; and 2) a deleterious arm due to increased mitochondrial ROS production through inhibition of autophagy by a Class I PI3‐kinase pathway in cardiomyocytes.

Support or Funding Information

Supported by NIH NS55008.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Flow Mediates Collecting Duct Histone Deacetylase 1 Nuclear Export
Authors: Sedaka Randee S. , Hyndman Kelly A. , Pollock Jennifer S.
Published: June 2021

Urinary flow within the renal tubules, especially the inner‐medullary collecting duct (IMCD), increases after high sodium consumption. We previously reported that this natriuretic response is due, in part, to elevated nitric oxide (NO) production without associated changes in NO synthase (NOS) expression. This suggests that high flow increases NO production via increased NOS activity. Histone deacetylase 1 (HDAC1) has recently been cited as a flow‐responsive protein and may post‐translationally deacetylate lysines on non‐histone proteins. Therefore, we hypothesized that flow‐mediated increases in NO production occur via HDAC1. Mouse IMCD cells were grown to confluency on glass slides, then placed under static conditions or 10 dynes/cm2 fluid‐flow for 1 hour at 37°C in the presence of vehicle (0.1% DMSO) or MS‐275 (300 nM), HDAC1‐selective inhibitor. Nitrite production, analyzed by HPLC, increased in response to flow >5‐fold (static: 231.4±31.1, flow: 1291.49.2±183.8 pmol/mg pr/hr; n=7/group, p<0.0001). MS‐275 significantly decreased NO production in response to flow (MS‐275: 342.8±44.0 pmol/mg pr/hr; n=9/group, p<0.0001). HDAC1 expression (static: 1.00±0.2, flow: 0.98±0.1 RDU/β‐actin; n=6/group, p>0.05) and activity (static: 1.00±0.06, flow: 0.85±0.02 RDU/β‐actin; n=3/group, p>0.05) was unchanged with flow in whole cell lysate. However, HDAC1 immunofluorescent staining of post‐flow IMCD cells suggested the presence of both nuclear and cytosolic HDAC1 and nuclear extraction of these flowed samples revealed a significant decrease in nuclear HDAC1 expression (static: 1.00±0.1, flow: 0.68±0.1 RDU; n=6/group, p<0.05), indicating nuclear export. Calcium, a key player in classical NOS activation, has also been reported to activate HDAC nuclear export. Thus, we further hypothesized that flow activation of NO production as well as flow‐mediated export of HDAC1 is calcium‐dependent. Flow‐induced NO production was abolished in the absence of calcium (flow+vehicle: 2038.1±402.0; flow+BAPTA: 377.7±75.3 pmol/mg pr/hr; flow+calcium‐free media: 474.8±133.2 pmol/mg pr/hr; n= 5–11/group, p<0.001). However, flow mediated nuclear HDAC1 export was similar in the presence and absence of BAPTA treatment (flow: 0.75±0.04, flow+BAPTA: 0.74±0.03 RDU; n=6/group, p>0.05). In conclusion, IMCD NO production in response to flow is both calcium‐ and HDAC1‐dependent, but extracellular calcium appears not to facilitate the flow‐mediated nuclear export of HDAC1. Further studies will elucidate the disparate mechanism(s) of flow‐mediated HDAC1‐dependent NO production from flow‐mediated HDAC1 nuclear export.

Support or Funding Information

This work was supported by funding from the National Institutes of Health ‐ P01 HL136267 to Dr. Jennifer Pollock and F31 DK111067 to Randee Sedaka.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Oxidative Stress During Simulated Hemorrhage Elicited by Lower Body Negative Pressure
Authors: Park Flora S. , Kay Victoria L. , Anderson Garen K. , Sprick Justin D. , Rickards Caroline A.
Published: June 2021

Background

Hemorrhage is a leading cause of potentially preventable death in both civilian and military trauma settings. Hemorrhage also elicits an oxidative stress response as a direct result of losing blood volume, or as an indirect response to ischemia‐reperfusion injury. Lower body negative pressure (LBNP) is a well validated, non‐invasive, and reproducible approach to simulate hemorrhage by inducing central hypovolemia in healthy conscious humans. The oxidative stress response to simulated hemorrhage via LBNP has not been quantified. We hypothesized that systemic markers of oxidative stress would increase with application of LBNP.

Methods

15 healthy human subjects (11M, 4F; 27 ± 1 y) were recruited for a step‐wise LBNP exposure to presyncope (systolic blood pressure <80 mmHg or subjective presyncopal symptoms). After baseline, LBNP pressure progressively decreased every 5 minutes to −15, −30, −45, −60, −70, −80, −90, and −100 mmHg. Arterial pressure and stroke volume were measured continuously via finger photoplethysmography, and venous blood samples were collected at baseline and during the LBNP profile. Plasma samples were analyzed for F2‐isoprostanes, a global marker of oxidative stress, via gas chromatography/mass spectrometry.

Results

The magnitude of central hypovolemia, indexed by the % change in stroke volume, ranged from a 27% to 74%. LBNP induced a −12.6 ± 2.6 % decrease in MAP (%Δ MAP) from baseline (P<0.001). F2‐isporostanes increased by 28.5 ± 11.6 % (P=0.05) from baseline (24 ± 2 pg/ml) to presyncope (29 ± 3 pg/ml). The increase in F2‐isoprostanes was not associated with the decrease in MAP (r=0.05).

Conclusion

Simulated hemorrhage elicited by step‐wise LBNP to presyncope elicited an increase in a global marker of oxidative stress. These findings have important implications in the study of hemorrhage and potential application of targeted interventions.

Support or Funding Information

Funding Source: Owens Foundation Grant and UNTHSC ICMD Junior Faculty Seed Grant.

Analysis of eicosanoids (F2‐isoprostanes) were performed in the Vanderbilt University Eicosanoid Core Laboratory.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Arginine Vasopressin Infusion In C57BL/6J Mice Induces Changes In The Placenta Transcriptome That Parallel Changes Observed In Placenta From Human Preeclampsia
Authors: Deng Guorui , Sandgren Jeremy A. , Keen Henry L. , Perschbacher Katherine J. , Zhang Shao Y. , Santillan Donna A. , Pierce Gary L. , Gibson‐Corley Katherine N. , Santillan Mark K. , Sigmund Curt D. , Grobe Justin L.
Published: June 2021

Preeclampsia (PE), a cardiovascular disorder of late pregnancy characterized by new onset hypertension and proteinuria, remains a devastating disease affecting approximately 10% of all pregnancies in the United States. Multiple independent studies demonstrate a correlation between PE and elevated maternal plasma copeptin, the C‐terminal fragment of arginine vasopressin (AVP), which supports the concept that AVP secretion is elevated during PE. Previously we demonstrated the sufficiency of chronic low‐dose AVP infusion to initiate major phenotypes of PE in pregnant C57BL/6J mice, including hypertension, renal glomerular endotheliosis, intrauterine growth restriction, and altered placental morphology. Thus, we generally hypothesize that elevated AVP secretion is mechanistically involved in the pathogenesis of PE. Here, we tested the hypothesis that chronic infusion of AVP during gestation in mice would cause changes in the placental transcriptome which parallel changes documented in human PE. Placentas were collected on gestational day 12.5 from mice that received chronic saline or AVP (24 ng/hr) infusion through pregnancy and RNA‐sequencing was performed. Differential expression analyses revealed 87 transcripts, corresponding to 82 unique genes as well as 3 non‐coding RNAs, that were differentially expressed between AVP‐ and saline‐treated placentas (FDR < 0.1). Among the differentially expressed genes identified, six genes (Trpm2, Itih4, Ncmap, Sema3f, Scnn1g, Nfat5) had been previously associated with human PE. Ingenuity Pathway Analysis (IPA) identified that the disease and functional annotations significantly altered in AVP‐treated placentas included hypertension, preeclampsia, as well as cell death. As expected, IPA also identified likely canonical upstream mediators including AVP, desmopressin, and calcium signaling. Notably, Gene Set Enrichment Analysis (GSEA) and IPA did not uncover any enrichment for hypoxia‐associated signaling, suggesting that despite the PE‐like morphological and genetic signatures induced by AVP, AVP does not induce these phenotypes via placental hypoxia. Parallel in silico re‐analyses of a large published dataset from NCBI‐GEO (GSE75010) describing the transcriptomes of control and PE human placentas with various clinical covariates demonstrated that some subtypes of human PE similarly do not exhibit placental hypoxia. Collectively, these data highlight molecular phenotypes of PE induced within the placenta of mice by AVP, and highlight the potential utility of the AVP infusion approach to model specific subtypes of human PE.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Respiratory load compensation and perception during 10‐breath sustained inspiratory resistive loading in normal subjects
Authors: Davenport Matthew Paul , Feinstein Justin , Khalsa Sahib , von Leupoldt Andreas , Davenport Paul Wesley
Published: June 2021

Increased load on the respiratory system is a key feature in various respiratory diseases, accompanied by ventilatory compensatory behavior and breathlessness. This increased inspiratory load is often prolonged, ranging from minutes to days, and requires the individual to adjust their breathing pattern to sustain alveolar ventilation and minimize the work of breathing, i.e. load compensation. Experimentally, this is often studied by breathing through resistive (R) loads. Most prior load compensation studies have used single breath loads within a range of adaptability for most individuals (0–40 cmH2O/l/s) to determine the load compensation mechanisms. However, during exacerbations of lung diseases, the individual must load compensate for multiple breaths against increasing load magnitudes that may exceed their ability to sustain alveolar ventilation. The aim of this study was to investigate load compensation in normal subjects when breathing for multiple breaths (10) through loads of increasing magnitudes greater than their expected ability to sustain alveolar ventilation. A threshold for load decompensation was hypothesized. Healthy participants were tested while breathing through a circuit with inspiratory flow‐resistive loads (R's: 0–100 cmH20/L/s). The loads were presented in random block order, each for 10 consecutive breaths and separated by unloaded breathing periods. The loads were presented in 2 trials, 2 times each per trial. Subjects estimated their perceived load intensity in one trial and unpleasantness in the other trial. A load compensation index (LCI) was calculated using breath phase duration and airflow. For R=0–25 cmH2O/L/s, respiratory load pattern was a load magnitude dependent increased maximum inspiratory pressure, decreased airflow, increased inspiratory duration and decreased expiratory duration. This resulted in a relatively constant total breath time, inspiratory volume, minute ventilation, PCO2, PO2 and LCI. However, decompensation was observed for R50 and R100 leading to declining minute ventilation and LCI. The results suggest, however, that increasing the duration of the R=50–100 load presentations would likely lead to hypoventilation and respiratory failure. The perception of inspiratory R load intensity and unpleasantness increased with load magnitude. The results suggest that high magnitude loads and/or long durations of loaded breathing result in increased affective response and decompensating respiratory pattern indicating that the individual is no longer able to sustain ventilation under these conditions.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effect of Agrimonia Pilosa Ledeb. on glucose tolerance and hepatic steatosis in ovariectomized rats fed high fat diet
Authors: Lee Young Min , Jang Hwan Hee , Park Mi‐Young , Bae Ji Hyun , Kim Jung Bong , Choi Jeong Sook , Kim Haeng Ran
Published: June 2021

Estrogen deficiency is associated with obesity, dyslipidemia, and increased insulin resistance in postmenopausal women. Development of an efficient therapeutic agent without side effects is needed to prevent or improve postmenopausal symptoms and diseases induced by estrogen deficiency. This study was performed to investigate the effects of water extract from Agrimonia pilosa Ledeb. on glucose and lipid metabolism in ovariectomized rats fed high fat diet. Female Sprague Dawley rats were sham operated or ovariectomized and after 3 weeks, assigned to the following groups: sham‐operated + high fat diet(S); ovariectomized + high fat diet (OVX); ovariectomized + high fat diet with 0.1% A. pilosa water extract (OVX+0.1A); ovariectomized + high fat diet with 0.5% A. pilosa water extract (OVX+0.5A). In our results, ovariectomy significantly increased body weight and dietary intake compare with sham group (p<0.05), however there was no significant difference in weight gain and dietary intake by A. pilosa treatment. Blood triglyceride, total‐cholesterol, and LDL‐cholesterol showed a tendency to decrease in A. pilosa supplemented groups. In glucose metabolism, we observed the blood glucose levels of the OVX+0.1A and OVX+0.5A groups were lower than those of the OVX group (p<0.05). Blood adiponectin concentration was also increased significantly by A. pilosa treatment in ovariectomized group (p<0.05). Additionally, we investigated the suppressive effect of A. pilosa aqueous extract on hepatic lipid accumulation. These effects were accompanied by reduced hepatic tissue expression of steatosis‐related genes. These data suggest that A. pilosa improves glucose tolerance and hepatic steatosis in ovariectomized rats.

Support or Funding Information

This study was supported by a research project of the National Institute of Agricultural Science of the Rural Development Administration, Republic of Korea (project no. PJ008554), and by the National Research Foundation of Korea(NRF) grant funded by the Korea government(MSIT) (No. 2017R1C1B5018328).

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Protective effect of Thymol essential oil from Thynus quinquecostatus extracts on UV irradiation‐induced skin aging by supressiong MMP‐1 expression and collagen degradation
Authors: Lee Tae Hoon , Jung Hana , Lee Sang Min , Park Yujin
Published: June 2021

Solar ultraviolet (UV) radiation is a main extrinsic factor for skin aging, which causes impairment of skin integrity through the induction of matrix metalloproteinases (MMPs), such as MMP‐1. Thynus quinquecostatus extracts are considered as potent anti‐photoaging agents due to including various active ingredients. To identify anti‐photoaging agents, in the present study, we examined preventing effect of thymol essential oil from Thynus quinquecostatus extracts on UV‐induced skin photo‐damage. First, we determined that the treatment concentration of without cytotoxicity on thymol by MTT assay in HaCaT cells. Next, we examined the attenuation of antiaging activity that the determined of MMP‐1 gene and protein expression levels in UVB‐induced keratinocyte. As a result, it was confirmed that the thymol and Thynus quinquecostatus extracts dramatically decreased UVB‐induced expression of MMP‐1 in a dose‐dependent manner. Our data showed that thymol and Thynus quinquecostatus extracts significantly attenuated UV‐induced phosphorylation of mitogen‐activated protein kinase (MAPK) signaling components ERK1/2, JNK1/2, and p38 proteins. This result suggests that the ERK1/2 kinase pathways likely contribute to the inhibitory effects of thymol and Thynus quinquecostatus extracts on UV‐induced MMP‐1 production in human keratinocytes. Taken together, our findings suggest that tymole essential oil from Thynus quinquecostatus extracts is a protective agent for skin anti‐photoaging through the prevention of UV‐induced MMP‐1 production.

Support or Funding Information

Funding from the Region Industry Total Information Service Program (R0004665), Republic of Korea, supported this work.

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 Physiological and Biomechanical Study about the Passive Diastolic Modelling of the Heart Failure Rabbits Causing by Aortic Arch Banding
Authors: Sun Xiaotong , Zhao Dongliang , Huo Yunlong , Tan Wenchang
Published: June 2021

Objective

Cardiovascular disease (CVD) is a major health problem world‐wide and can lead to congestive heart failure (HF). Aortic arch banding is a classic experimental scheme to establish the congestive HF model, when hypertension and cardiac hypertrophy occur to the rabbits. Left ventricular myofiber stress and strain analyzing is an effective biomechanical method to study congestive HF. Our target is to study the physiological and biomechanical behave of the congestive heart failure model.

Method

By aortic arch banding, we establish the heart failure model. 6 New Zealand white rabbits have been banded 30% at aortic arch. The rabbits are scanned by Computed Tomography after 2‐weeks and 4‐weeks separately. We developed a three‐dimensional finite element model, which can describe the rabbit ventricular geometry and fiber architecture in detail. At same time, the paraffin sections have be surveyed in pathology.

Result

The volumes of the hearts can be calculated by 3‐D reconstructed model, which range from 2338.99 mm3 (SD 84.06) at 2‐weeks to 3339.07 mm3 (SD 701.91) at 4‐weeks. The strain and stress get lower from 2‐weeks to 4‐weeks. A huge change can be found in pathology sections.

Conclusions

We find the changing pattern of the strain and stress. The law of heart failure in physiology and biomechanics were discussed.

Support or Funding Information

This research is supported in part by the National Natural Science Foundation of China Grant 11372010(Y Huo); Shenzhen Science and Technology Innovation Institution (China) Grant JCYJ20160427170536358 (Y Huo).

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 effects of core and skin temperatures and dehydration on heart rate response during interval exercise in warm and cool conditions
Authors: TAKEDA RYOSUKE , Imai Daiki , Kwai Eriko , Ota Akemi , Hanno Genta , Morita Emiko , Suzuki Yuta , Yokoyama Hisayo , Okazaki Kazunobu
Published: June 2021

Heart rate (HR) gradually increases during exercise at a constant work load, which is known as cardiovascular drift (CVD). The CVD is exacerbated when exercise is performed under condition with high ambient temperatures (Ta). It is suggested that increased esophageal temperature (Tes) is associated with the level of CVD. In the present study, we examined the effect of skin temperatures (Tsk) and the dehydration on CVD during high intensity interval exercise.

METHODS

Eight healthy young men underwent interval exercise on a cycling ergometer for 72 min (8 sets of 4 min at 80% VO2max – 5 min at 20% VO2max) in cool (Ta of 20□, 40% relative humidity) and warm (Ta of 30□, 40% relative humidity) conditions. Tes, Tsk, heart rate (HR), sweat rate (SR) and skin blood flow (SkBF) at chest were measured continuously. Blood samples were taken before and at the end of exercise, and relative change in plasma volume (%ΔPV) after exercise were determined from hematocrit and hemoglobin concentration of the blood samples.

RESULTS

HR increased during exercise at 80% VO2max while decreased during exercise at 20% VO2max in both trials. HR in warm condition was higher than cool condition (p < 0.05) throughout trial. More importantly, HR at the end of each set was gradually increased during exercise and the increase was significantly higher in warm than in cool condition. Tes increased during exercise at 80% VO2max while decreased during exercise at 20% VO2max in both trials, it reached the peak value at the end of the 4th set of exercise at 80% VO2max (37.93 ± 0.04□ (means ± SE) in cool and 37.84 ± 0.04□ in warm), then kept these values until the end of trial. There was no significant difference in Tes between trials throughout trial. Tsk was higher (p < 0.05) in warm than cool condition throughout trial. SR at chest was higher (p < 0.05) in warm than cool condition from 9 min to the end of exercise, while SkBF at chest was not significantly different between conditions throughout trial. The %ΔPV was not different among conditions (−13.9 ± 1.0 % in cool, −12.7 ± 1.5 % in warm).

CONCLUSIONS

Exercise in a warm condition increased HR during interval exercise compared to a cool condition despite the level of esophageal temperature and dehydration were same between conditions. The increased HR would be associated with an increased skin temperatures.

Support or Funding Information

This work was supported by a Grant‐in‐Aid for Scientific Research (B) and a Grant‐in‐Aid for Challenging Exploratory Research (K. Okazaki) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effects of Transcutaneous Carbon Dioxide (CO2) on Hyperglycemia‐Induced Capillary Regression in Skeletal Muscle
Authors: Matsumoto Tomohiro , Takuwa Miho , Hirabayashi Takumi , Ikeji Takuya , Ono Kohei , Maeshige Noriaki , Kondo Hiroyo , Fujino Hidemi
Published: June 2021

Hyperglycemia causes microvascular impairment in skeletal muscle of diabetes. Transcutaneous carbon dioxide (CO2) have been shown to increase capillary in skeletal muscle of healthy rats via the increase of angiogenic factor. The purpose of this study was to determine the effects of transcutaneous CO2 on muscle capillary impairment by exposure of hyperglycemia in streptozotocin (STZ)‐treated diabetic rats. Twenty‐four male Wistar rats (220~270g) were divided into control (CON), CO2, STZ and STZ+CO2 groups. STZ (50 mg/kg) was injected into the tail vein of rats. Blood glucose levels above 250 mg/dl after 2 days of the STZ injection confirmed the diabetic state. The lower limbs in rats were shaved and hydrogel was applied afterwards. The CO2 adaptor was attached to the limbs and sealed, and CO2 was administered into the adaptor for 30 min. This treatment was performed 5 days per week for 8 weeks. STZ resulted in capillary regression, indicated by decreases in capillary‐to‐fiber ratio. However, the capillary‐to‐fiber ratio in STZ + CO2 was higher than that in STZ. In addition, the protein expression level of vascular endothelial growth factor (VEGF), which is angiogenic factor, in STZ + CO2 was higher than that in STZ. The protein expression level of thrombospondin‐1 (TSP‐1), which is antiangiogenic factor, in STZ + CO2 was lower than that in STZ. These results indicated that transcutaneous CO2 attenuated the capillary regression via the increase of angiogenic factor and the decrease of antiangiogenic factor.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Increased Subpleural Pulmonary Arteriolar Tone Associated with Inhibition of Nitric Oxide Synthase in a Mouse Model of Type‐1 Diabetes
Authors: Roberts Andrew M. , Jagadapillai Rekha , Moulana Nayeem , Cai Lu , Gozal Evelyne
Published: June 2021

Type‐1 diabetes, characterized by elevation of blood glucose, inflammation and oxidative stress, results in endothelial injury that alters nitric oxide (NO) signaling and impairs microvascular regulation in a variety of vascular beds. NO signaling also plays a prominent role in the modulation of alveolar perfusion. Therefore, the lungs may be particularly vulnerable to diabetes‐induced endothelial changes. We hypothesized that diabetes‐induced oxidative injury, resulting in decreased NO bioavailability and enhanced fibrinogen‐endothelial interaction, induces endothelial injury and pulmonary microvascular dysfunction in the mouse lung. The effects of acute NO synthase (NOS) inhibition with L‐NAME on subpleural arterioles were examined in streptozotocin‐treated C57BL/6J mice (STZ) and their saline‐treated controls (Control). Microvascular changes were assessed by intravital microscopy of the right lung in anesthetized mice (7 to 11 months old) with open chest and ventilated lungs. Pulmonary arteriolar diameters (ranging from 27.2 – 48.7 μm) were measured before and after acute administration of the nitric oxide synthase (NOS) inhibitor, L‐NAME (0.1mg/g body wt). L‐NAME caused a 13.6 ± 7.5% constriction (n=5, p=0.034) in Control mice. In contrast, there was an 18.0 ± 11% dilation (p<0.009, n=5) in STZ mice. Intra‐arterial administration of fluorescently‐labeled fibrinogen in STZ mice, without L‐NAME treatment, resulted in adherence of fibrinogen in the microvascular network, indicating endothelial injury. These data suggest that diabetes‐induced systemic effects may affect lung endothelial function. Control mice displayed a physiological vasoconstriction response to L‐NAME resulting from a loss of the NO vasodilator influence. In contrast, while L‐NAME may have decreased bioavailable NO in the diabetic lung, inhibition of NOS with L‐NAME appeared to have a vasodilator effect by decreasing formation of reactive nitrogen species or by unmasking another vasodilator. We conclude that diabetes may adversely affect lung microvasculature by inducing inflammation and decreasing NO bioavailability. Altered NO‐induced responses may subsequently cause significant pulmonary endothelial injury and microvascular dysfunction that could lead to ventilation‐perfusion abnormalities and exacerbate systemic complications of diabetes

Support or Funding Information

University of Louisville, School of Medicine Collaborative Enhancement Grant

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.