bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Fitness on Vascular Function in Young Adults during Acute Inflammation
Authors: Schroeder Elizabeth C , Hilgenkamp Thessa I.M. , Lefferts Wesley K , Baynard Tracy , Fernhall Bo
Published: June 2021

Acute inflammation is associated with increased risk of cardiovascular events and impairs vascular function. Vascular function in this setting is most often interrogated by assessing endothelial function in conduit arteries, however, less is known regarding the downstream vascular tree including resistance artery and microvasculature function. Vascular dysfunction during acute inflammation may be attenuated by high cardiorespiratory fitness due to its association with improved vascular function and cardiovascular health.

PURPOSE

Determine the effect of acute inflammation and fitness on conduit artery, resistance artery, and microvascular function.

METHODS

Vascular function was assessed in 11 low fit (6 male, 24 ± 5 yrs, 22.8 ± 4.3 kg/m2, 34.5 ± 2.9 ml/kg/min) and 12 high fit (5 male, 27 ± 4 yrs, 22.6 ± 1.9 kg/m2, 56.4 ± 9.7 ml/kg/min) participants at baseline and 24h after a typhoid vaccination. Fitness was determined using a maximal treadmill test and those with a VO2peak >75th age‐ and sex‐specific percentile according to the American College of Sports Medicine were considered high fit. Vascular assessments included flow‐mediated dilation (FMD) of the brachial artery via ultrasonography, forearm reactive hyperemia (RH) via venous occlusion plethysmography, and near‐infrared spectroscopy (NIRS) during a 5‐min arterial occlusion. Blood pressure was measured using an oscillometric cuff and C‐reactive protein (CRP) and interleukin‐6 (IL‐6) were assessed via standard ELISA techniques.

RESULTS

Acute inflammation was induced, as evident by increases in IL‐6 and CRP (p<0.01, see Table). Mean arterial pressure did not change in either group (low fit: 92 ± 9 to 91 ± 8; high fit: 92 ± 10 to 91 ± 7). FMD was lower in the high fit group, yet both groups reduced FMD at 24h, even after controlling for shear rate (p<0.05). No effect of acute inflammation was observed for forearm RH or NIRS (p>0.05). High fit individuals, however, had greater microvascular reactivity with a quicker ability to accommodate increased blood flow (time to peak, group effect, p<0.05).

CONCLUSION

Fitness did not alter the vascular response to acute inflammation, regardless of the level along the vascular tree. Both groups showed reductions in conduit artery endothelial function and no change in resistance artery or microcirculatory function, suggesting acute inflammation has non‐uniform effects on vascular function. Cardiorespiratory fitness did not influence the arterial response to inflammation, at least in this young, healthy population. Future studies need to evaluate the effects of acute inflammation in older individuals including those who are healthy and those with chronic health conditions.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
High‐endothelial cell‐derived S1P regulates dendritic cell localization and vascular integrity in the lymph node
Authors: Simmons Szandor , Sasaki Naoko , Umemoto Eiji , Uchida Yutaka , Fukuhara Shigetomo , Kitazawa Yusuke , Okudaira Michiyo , Inoue Asuka , Tohya Kazuo , Aoi Keita , Aoki Junken , Mochizuki Naoki , Matsuno Kenjiro , Takeda Kiyoshi , Kuebler Wolfgang M. , Miyasaka Masayuki , Ishii Masaru
Published: June 2021

While the sphingosine‐1‐phosphate (S1P)/sphingosine‐1‐phosphate receptor‐1 (S1PR1) axis is critically important for lymphocyte egress from lymphoid organs, S1PR1 activation also occurs in vascular endothelial cells (ECs), including those of the high‐endothelial venules (HEVs) that mediate lymphocyte immigration into lymph nodes (LNs). To understand the functional significance of the S1P/S1PR1‐Gi axis in HEVs, we generated Lyve1‐Spns2Δ/Δ conditional knockout mice for the S1P‐transporter Spinster‐homologue‐2 (Spns2), as HEVs express Lyve1 during development. In these mice, HEVs appeared apoptotic and were severely impaired in function, morphology and size; leading to markedly hypotrophic peripheral LNs. Within these LN, dendritic cells (DCs) were unable to interact with HEVs, which was also observed in VEcad‐CREERT2‐S1PR1Δ/Δ mice and wildtype mice treated with S1PR1‐antagonists. Wildtype HEVs treated with S1PR1‐antagonists in vitro, as well as Spns2‐deficient HEVs in vivo, show severely reduced release of the DC‐chemoattractant CCL21. Together, our results reveal that EC‐derived S1P warrants HEV‐integrity through autocrine control of S1PR1‐Gi signaling, and facilitates concomitant HEV‐DC interactions.

Support or Funding Information

This work was supported by Grants‐in‐Aid for Scientific Research (A) from the Japan Society for the Promotion of Science (JSPS; JP25253070 and JP16H02619 to M.I.); Grants‐in‐Aid for Young Scientists (B) from the JSPS (JP26860329 to S.S.); grants from the Takeda Science Foundation (to M.I.); from the Uehara Memorial Foundation (to M.I.); from the Kanae Foundation for the Promotion of Medical Sciences (to M.I.); and from the Kishimoto Foundation (to S.S.).

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Platelets determine the onset of innate and adaptive immune cell responses Schaubaecher J, Mittmann L, Uhl B, Reichel CA
Authors: Schaubächer Johanna
Published: June 2021

Neutrophils represent the first immune cells recruited to the site of injury or infection, followed by monocytes and, later on, lymphocytes. In addition to their fundamental role in hemostasis, platelets are increasingly recognized to serve as critical modulators of immune responses. Whereas interactions of platelets with myeloid leukocytes have been extensively studied, the functional relevance of these cellular blood components for the regulation of lymphocyte trafficking remains poorly understood. Employing multi‐channel in vivo microscopy on the mouse cremaster muscle, platelets were found to instantly accumulate in the venular microvasculature upon induction of inflammation right before neutrophils, monocytes, and lymphocytes, but are progressively released from the endothelium into the bloodstream after extravasation of myeloid leukocytes. In this context, platelets divergently control the trafficking of myeloid leukocytes and lymphocytes to inflamed tissue as assessed by multi‐channel flow cytometry analyses in a mouse peritonitis assay: Whereas depletion of platelets severely compromised the extravasation of neutrophils and classical monocytes, the recruitment of CD4+ lymphocytes, CD8+ lymphocytes, and B lymphocytes to the perivascular space was dramatically enhanced. Importantly, depletion of neutrophils in these experiments completely abolished responses of classical monocytes, but did not affect lymphocyte trafficking. In this context, activated platelets were found to upregulate surface expression of adhesion/signaling molecules facilitating interactions with neutrophils such as CD40 and CD40L as well as of factors interfering with lymphocyte activation including programmed death‐ligand 1 (PD‐L1), CD80, and CD86. Blockade of these latter immune checkpoint molecules significantly enhanced lymphocyte responses to the level of platelet‐depleted animals. Thus, our experimental data identify a previously unappreciated functional role of platelets as ‚decision makers' in the immune system that critically regulate the onset of innate and adaptive immune cell responses in inflammatory reactions.

Support or Funding Information

This study was supported by Deutsche Forschungsgemeinschaft (DFG), Sonderforschungs‐bereich (SFB) 914.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Zika Virus Localizes to Vascular Endothelial and Smooth Muscle Cells following In Vivo Infection
Authors: Peruri Alekhya , Brown Isola A.M. , Wang Tony T. , Isakson Brant E.
Published: June 2021

Zika virus (ZIKV) is a public health concern due to its classification as a bloodborne pathogen. However, the pathology of ZIKV— i.e. its mechanisms of infection – is not been fully understood. We and other researchers have recently discovered that multiple ZIKV strains readily infect primary human endothelial cells (ECs). However, the cellular targets of the virus during in vivo whole animal infection are not known. We investigated the role of the intact vasculature in ZIKV infection and hypothesized that ZIKV will be localized to ECs following in vivo infection.

7‐week old male C57Bl/6 mice were treated using an established in vivo animal model of ZIKV infection. Mice received ZIKV strains isolated from either an African (DAK) or South American (PRV) viral outbreak. Mice were sacrificed 7 days post‐infection and we used immunohistochemistry to detect ZIKV expression in collected vessels including the aorta, mesenteric arteries and veins, the renal artery, and the cremasteric and retinal vasculatures. ZIKV virus was labeled anti‐4G2, which marks a viral coat protein of ZIKV, and ECs were labeled with anti‐CD31.

Mice treated with the DAK strain showed positive localization in the smooth muscle cells (SMCs) of the cremaster preparation, ECs of mesenteric vessels, and SMCs and ECs of the renal artery. Those treated with the PRV strain also showed localization in the ECs of the cremaster and mesenteric vasculatures, and both the SMCs and ECs of the renal artery. There was no positive ZIKV localization found in the retina.

Positive localization of ZIKV in the vascular beds of the cremaster, mesenteric vessels, and renal artery suggests a role for the ECs and SMCs of the vasculature in the pathology of ZIKV infection. Future work will investigate key cellular targets that may be in involved in regulating in vivo ZIKV infection, such as the AXL tyrosine kinase receptor AXL which is required for ZIKV infection in vitro. These and future studies will improve our understanding of the pathology of ZIKV infection.

Support or Funding Information

Ford Foundation Postdoctoral Grant (IAMB), HL 088554 R01 (BEI)

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Traumatic Brain Injury Alters BK Channel Subunit Expression, Localization, and Function in Cerebral Arterial Myocytes
Authors: Evanson Kirk W. , Goldsmith Jacob A. , Ghosh Payal , Levenson Cathy W.
Published: June 2021

Traumatic brain injury (TBI) induces acute changes in cerebrovascular function, which include alterations to cerebral artery myogenic tone and autoregulation. In arterial smooth muscle cells (myocytes), large‐conductance calcium‐activated potassium (BK) channels play a vital role in modulating plasma membrane potential and myogenic tone. Here, we examined BK channel expression and function in cerebral resistance size arteries one week following moderately‐severe TBI induced by controlled cortical impact with craniotomy. Total BKα (pore‐forming) and β1 (regulatory) subunit expression were reduced one week post‐TBI. Biotinylation of plasma membrane‐bound proteins revealed a compensatory increase of β1 subunits to the plasma membrane following TBI, which normalized single BK channel activation as assessed using patch‐clamp electrophysiology. However, the loss of total BKα subunits resulted in diminished whole cell, transient BK currents. Pressurized cerebral arteries from TBI rats exhibited greater myogenic tone at 60 mmHg and a diminished response to iberiotoxin, a BK channel pore blocker. In conclusion, moderately‐severe TBI enhances cerebral artery contractility, in part, through reductions in arterial myocyte BK channel subunit expression and function. Moreover, these TBI‐induced alterations in cerebral artery function can persist well beyond the initial 24–48 hour period post‐injury.

Support or Funding Information

Florida State University

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Thyroid Hormone Deficiency Adversely Affects Cardiomyocyte T‐tubule Structure and Function
Authors: Zolotareva Natalie , Weick Rose‐Ann , An Shimin , Lee Jae S. , Zhang Youhua , Gerdes A. Martin , Ojamaa Kaie
Published: June 2021

Thyroid hormone deficiency causes adverse changes in cardiomyocyte shape leading to increased wall stress, chamber dilatation and in the long‐term can result in heart failure. We hypothesized that thyroid hormones regulate cardiac contractile function in part by maintaining T‐tubule (TT) structures and efficient excitation‐contraction (EC)‐coupling.

Methods

Female Sprague‐Dawley rats (aged 12 wks) were surgically thyroidectomized (Tx) or were maintained as euthyroid (Eu) controls (6 rats/group). The study was terminated after 12 mo. at which time echocardiographic and hemodynamic measurements were recorded. Ventricular myocytes were isolated by collagenase digestion and plated onto laminin‐coated glass coverslips for TT analysis or were analyzed immediately for contractile and calcium dynamic using videobased edge detection of sarcomere length changes coupled to a fluorescence imaging system (IonOptix). Live cells were labeled with wheat germ agglutinin‐coupled to Alexa‐Fluor (WGA‐488) to image the sarcolemma and TT by confocal microscopy. Multiple z‐stack images were captured per cell and TT periodicity was analyzed using an algorithm to calculate periodicity based on the peak amplitude in the Fourier spectrum of the image at the TT frequency, or TT power. This software program is available as TTorg plugin on ImageJ.

Results

Echocardiography and in vivo hemodynamic measurements showed significantly reduced systolic and diastolic function in Tx vs euthyroid rats. In response to 1 Hz field stimulation at 4V, isolated cardiomyocyte contractile cycles showed significant dysfunction in Tx vs Eu cardiomyocytes: slower max contraction velocity (+Vmax), −2.047±0.30 vs −3.503±0.50 um/sec, Tx vs Eu, respectively, p<0.001; slower max relaxation velocity (‐Vmax), 1.369±0.27 vs 2.44±0.73 um/sec, p<0.01; longer time to peak contraction, 0.279±0.03 vs 0.182±0.03 sec, p<0.001. Myocytes were loaded with Fura2/AM (1uM) and intracellular calcium measured by fluorescence intensity ratio at 340/380 nm. Ca2+ transients showed slower kinetics in Tx vs Eu cardiomyocytes: time to Ca2+ peak, 0.076±0.01 vs 0.0516±0.003 sec, Tx vs Eu, respectively, p<0.0001; time to Ca2+ max return velocity, 0.261 0.03 vs 0.184 0.005, Tx vs Eu, respectively, p<0.0001. TTorg analysis indicated significant disorganization of T‐tubules in Tx cardiomyocytes compared to Eu (TT power = 61±2 vs 80±2, Tx vs Eu, respectively, p<0.00001; arbitrary units with higher values indicate increased periodicity). In conclusion, TH‐deficiency disrupts T‐tubule structures causing cardiomyocyte contractile dysfunction and slower calcium kinetics indicating altered EC‐coupling. Therefore maintaining normal thyroid function is necessary for optimal heart 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.
Elucidating the Physiological Role of Mitochondrial ETC Supercomplexes in the Heart
Authors: Chapa‐Dubocq Xavier R , Rodriguez‐Graciani Keishla Marie , Guzman‐Hernandez Roberto Alejandro , Jang Sehwan , Javadov Sabzali
Published: June 2021

Background

For a long time, mitochondrial electron transport chain (ETC) complexes was thought to function as separate entities. However, studies conducted in the past decade revealed that individual ETC complexes can assemble to form supramolecular structures known as supercomplexes (SCs). The SCs, particularly respirasome are composed of the ETC complexes I, III and IV in various stoichiometry. The respirasome is considered to play an important role in facilitating electron transport, reducing ROS production, and maintaining structural integrity of individual ETC complexes. Despite extensive studies on the molecular identity, the physiological role of SCs in cells, particularly, in high energy‐consuming organs such as the heart and brain remain unknown. These studies seek to determine whether disassembly of SCs affects the cardiac function in rats.

Methods

Hearts isolated from Sprague Dawley rats (275–325g) were perfused with Krebs Henseleit solution (KHS) via the Langendorff‐perfusion model. Experimental groups were as follows: (i) perfusion for 40 min with KHS, (ii) perfusion for 20 min with KHS and 20 min with rotenone (an inducer of SC dissociation) (n=8), (iii) perfusion for 60 min with KHS (n=4), (iv) perfusion for 20 min with KHS followed by 20 min perfusion with rotenone and 20 min with KHS (washout, no rotenone) (n=6). In control groups (i) and (iii), ethanol was as a vehicle in concentration used for rotenone groups [(ii) and (iv)]. In addition, we compared SC levels in mitochondria isolated from non‐perfused hearts (v), and hearts perfused with KHS (vi) containing no vehicle (ethanol) with those in i–iv groups. Cardiac function was monitored throughout the entire perfusion period. At the end of each protocol, the mitochondria were isolated for analysis of SCs, permeability transition pore opening, respiration rates and ROS production.

Results

Cardiac function between rats perfused with KHS (vi) and ethanol (i and iii) had no significant difference, though rotenone perfused rats (ii and iv) had a significant reduction (< 40%) in cardiac function. Mitochondrial respiration data shows a significant reduction in complex I oxygen consumption rate in rotenone perfused (ii and iv) rats. Analysis of SCs by blue native PAGE displayed a significant reduction in SC levels in both ethanol (i and iii) and rotenone (ii and iv) perfused rats in comparison to hearts perfused with KHS (vi) alone. No significant differences in SC levels were found between the ethanol (i and iii) and rotenone (ii and iv) perfused groups.

Conclusion

Our data demonstrate lack of causal relationship link between mitochondrial ETC SCs and cardiac function in rats.

Support or Funding Information

Supported by the NIGMS NIH grants SC1GM128210 and R25GM061838

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Impact of Spinal Cord Injury and Chronically Induced Orthostatic Hypotension on Left Ventricular Contractility and Stiffness
Authors: Hayes Brian , Poormasjedi‐Meibod Malihe‐Sedat , Fossey Mary , Erskine Erin , Gupta Rishi , Granville David J , Phillips Aaron A , West Christopher R
Published: June 2021

Introduction

Complete spinal cord injury (SCI) above the T3 spinal level is associated impaired left ventricular (LV) systolic function. However, the effect on diastolic structure and function has yet to be examined. Furthermore, high thoracic SCI impairs centrally‐derived cardiovascular responses to postural change, leading to the development of orthostatic hypotension (OH) post‐SCI. While it has been demonstrated that these frequent bouts of OH cause impairments in cerebrovascular function, it is not known whether this hemodynamic instability also impairs cardiac function.

Methods

This study examined the effect of SCI on LV systolic and diastolic function in the presence or absence of daily bouts of acutely induced OH. 22 rats were divided into four groups: 1. Rats with a sham injury and no daily OH (SHAM, n=5), 2. Rats with a sham injury and daily induced OH (SHAM‐OH, n=6), 3. Rats with a complete T3 transection injury and daily induced OH (T3‐OH, n=5), 4. Rats with a complete T3 transection and no daily OH (T3‐SCI, n=6). 9 weeks after surgery, LV pressure‐volume (PV) catheterization was performed to assess LV basal PV indices, as well as cardiac contractility and stiffness. Furthermore, the coupling of the arterial system and the left ventricle was characterized to examine the influence of SCI and/or OH on the efficiency of the interaction between the LV and arterial system.

Results

Compared to both SHAM and SHAM‐OH, the T3‐SCI and T3‐OH groups experienced significant reductions in systolic blood pressure, LV stroke work and cardiac output (all p<0.023). The T3‐OH group demonstrated an increase in arterial elastance compared to both the SHAM‐OH and SHAM groups (p<0.014). T3‐SCI and T3‐OH groups exhibited reduced end‐systolic elastance compared to both SHAM and SHAM‐OH (p<0.04). No difference was found in LV stiffness between the four groups. Finally, the ratio of ventricular‐vascular coupling was found to be significantly increased in the T3‐OH group compared to all other groups (all P<0.019).

Conclusion

Complete high thoracic and cervical SCI causes a reduction in LV contractile function. Combined high thoracic SCI and daily OH impairs ventricular‐vascular coupling via changes in arterial compliance.

Support or Funding Information

Heart and Stroke Foundation of Canada (HSFC), International Collaborations on Repair Discoveries (ICORD), Natural Sciences and Engineering Research Council of Canada (NSERC), Blusson Integrated Cures Partnership (BICP).

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
A Revised Pulmonary Artery Constriction Model of Right Ventricle Failure in Adult Ovine
Authors: Nguyen‐Truong Michael , Liu Wenqiang , Boon June , Nelson Brad , Easley Jeremiah , Monnet Eric , Wang Zhijie
Published: June 2021

Introduction

Right ventricle failure (RVF) is associated with serious cardiac and pulmonary diseases that contribute significantly to the morbidity and mortality of patients [1]. Currently, the mechanisms of RVF are not fully understood and it is partly due to the lack of large animal models to investigate the pathogenesis that includes biomechanical properties and mechanobiology of the RV [2,3]. In this study, we aim to establish an adult ovine model of RVF to examine the hemodynamic, structural and mechanical adaptations of the RV under chronic pressure overload.

Methods

All procedures were approved by Colorado State University IACUC. To induce RV pressure overload, ~8‐month old male sheep underwent a revised method of pulmonary artery constriction (PAC) by patient‐specific, repeated filling of an adjustable hydraulic occluder (Norfolk Vet Products, IL) with saline at week 0, 1, and 4. The amount of saline injected was determined to acutely elevate the RV pressure to be comparable to its own left ventricle pressure. Healthy, age‐matched male sheep were used as controls (CTL). Echocardiography was performed in awake animals at baseline (week 0) and 2, 4, 6, 8, and 11 weeks post PAC. On week 11, animals were anesthetized and catheterized with Swan‐Ganz and pressure‐volume (PV) catheters to obtain hemodynamic measurements. Finally, hearts were extracted and tissue thickness and weight were measured. RV hypertrophy was quantified by RV wall thickness using a caliper and Fulton's index as the weight of RV/(LV+Septum). One‐way ANOVA with repeated measures and Dunnett's post hoc tests were performed to examine RV changes over time. Unpaired Student's t‐test was performed between the CTL and PAC groups. p<0.05 was considered statistically significant compared to baseline (week 0) or CTL.

Results

The new PAC methodology resulted in a marked increase in RV systolic pressure (RVSP) and decreases in stroke volume and tricuspid annular plane systolic excursion (TAPSE) at week 11 (Fig. a–c). During the PAC period, impaired ejection dynamics was observed by a gradual decrease of the ratio of acceleration time to ejection time (AT/ET) (Fig. d). Significant increases in Fulton's index and RV free wall thickness suggested RV hypertrophy under PAC (Fig. e–f). The systemic circulation and LV were not affected and functioned normally (data not shown).

Conclusion

The revised patient specific, repeated PAC method provided an easy and robust approach to induce RVF secondary to pressure overload. The development of RVF was evident by changes in RV structure and function as described above. The histological and mechanical changes will be further investigated. This ovine model will offer a useful tool to study the progression and treatment of RVF in large animal species.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Cardiac and Renal Function Interactions in Heart Failure with Reduced Ejection Fraction: A Mathematical Modeling Analysis
Authors: Yu Hongtao , Hallow Melissa Karen
Published: June 2021

Congestive heart failure is characterized by suppressed cardiac output (CO) and arterial filling pressure, leading to renal retention of salt and water, contributing to further volume overload and dysfunction. It remains a challenge to understand or predict the interplay between the heart and kidneys especially when one of them is in a state of dysfunction. Mathematical modeling provides a means to investigate the acute and chronic functional feedback between the organs. In the current work, two mechanistic mathematical models of cardiac and renal function, previously reported separately, were integrated to simulate the physiological relationships between cardiac and renal function. The two models were linked as follows: 1) mean arterial pressure (MAP) and venous pressure determined from the cardiac model serve as input to the renal model, 2) sodium and water excretion in the kidney model determines extracellular fluid volume in the cardiac model, and 3) the exchange of the fluid between the blood volume (BV) and interstitial fluid volume (ISFV) through capillary membrane was considered via starling forces. By adjusting the heart contractility, arterial stiffness, and systemic resistance, the main pathophysiological features of heart failure with reduced ejection fraction (HF‐REF) could be reproduced: decreased ejection fraction, elevated and gradually increasing BV and ISFV, elevated end diastolic pressure of the left ventricle, and loss of cardiac reserve. Quantitatively, agreement with the clinical characteristics of healthy and HF‐REF subjects seemed to support the proposed cardio‐renal model in capturing the physiological features. The cardio‐renal model can also reproduce the improvements in HF‐REF function with Angiotensin‐Converting‐Enzyme inhibitor (ACEi) as reported in the SOLVD clinical trial. This model has the potential to provide insights into the mechanisms by which pharmacologic targets in the kidney alter or improve cardiovascular function in heart failure.

Support or Funding Information

This research was funded by AstraZeneca

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Ethnic difference in nighttime melatonin can partially explain the ethnic difference in nighttime blood pressure: A study in European Americans and African Americans
Authors: Wang Xiaoling , Zhu Haidong , Harris Ryan , Dong Yanbin , Su Shaoyong , Tingen Martha , Kapuku Gaston , Pollock Jennifer , Pollock David , Harshfield Gregory
Published: June 2021

Background

Blood pressure (BP) follows a diurnal pattern which is regulated by circadian clock. Epidemiological studies have demonstrated that nighttime BP is a stronger predictor of cardiovascular morbidity and mortality compared to daytime BP. Ethnic differences in nighttime BP have long been documented with African Americans (AAs) having higher pressures than European Americans (EAs). Recently, lower nighttime melatonin, a neurohormone in the superachiasmatic nucleus and key regulator of the central circadian clock, has been associated with higher nighttime BP levels in EAs. However, whether or not ethnic difference exists in nighttime melatonin secretion is unknown. This study sought to test the hypothesis that AAs will have a lower nighttime melatonin secretion compared with EAs and this ethnic difference in melatonin can at least partially explain the ethnic difference in nighttime BP.

Methods

A total of 150 young adults (71 AA and 79 EA; mean age: 27.7 years old; age range: 20.5–35.9 years old, 46% females) enrolled in visit 15 of the Georgia Stress and Heart study provided an overnight urine sample for the measurement of 6‐sulfatoxymelatonin, the major metabolite of melatonin. Urine melatonin excretion (UME) was calculated as the ratio between 6‐sulfatoxymelatonin concentration and creatinine concentration. Twenty‐four‐hour ambulatory BP was measured in all participants and nighttime systolic BP (SBP) was used as a major outcome of BP regulation.

Results

After adjustment of age, sex and body mass index, AAs had significantly lower UME (AAs vs EAs: 0.26±0.20 vs 0.34±0.33; P=0.002) and higher nighttime SBP than EAs (AAs vs EAs: 110.0±10.2 vs 107.2±8.9 mmHg; P=0.036). Lower UME rate was significantly associated with higher nighttime SBP and this relationship did not depend on ethnicity. With a tertile increase in UME, mean nighttime SBP decreased 2.6 mmHg (P‐value for trend=0.011). The ethnicity difference in nighttime SBP was significantly attenuated after adding UME into the model (P for ethnicity=0.193). Mediation testing showed that 35.5% of ethnicity difference in nighttime SBP could be explained by UME (P=0.035).

Conclusion

The present study is the first to document the ethnic difference in nighttime melatonin excretion, suggesting that AAs have an impaired circadian rhythm and low melatonin secretion compared with EAs. Furthermore, the ethnic difference in nighttime melatonin can partially explain the established ethnic difference in nighttime SBP.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Cerebrovascular Consequences of Chronic Orthostatic Hypotension
Authors: Suraj Rejitha , Hodge Sarah , Spence Emma E.M. , Walsh Emma J. , Zhu Hai‐Lei , Sutherland Cindy , Turnbull Jeannine , Belke Darrell , Rosentreter Ryan E. , Soriano Jan Elaine , Scott Berkeley A. , Saddiq Ibrahim A. , Cole William C. , West Christopher , Phillips Aaron A.
Published: June 2021

Population‐level data indicates that people who chronically experience orthostatic hypotension have an elevated risk of cerebrovascular disease. We are unaware of experimental data to support these observations, and the mechanistic underpinnings of this population‐level association are yet to be understood. Here, we aimed to evaluate if chronic exposure to orthostatic hypotension impairs cerebrovascular function and structure.

We first developed a rodent model of orthostatic hypotension that resulted in a clinically‐relevant reduction in systolic blood pressure that was accompanied by hypo‐perfusion of the brain. Next, a group of animals were chronically exposed to repetitive orthostatic hypotension for five weeks, while a control group received standard care. Cerebrovascular function and structure were then evaluated using a variety of in vivo and in vitro methods.

Our results suggest that chronic exposure to orthostatic hypotension may impair the function and structure of the cerebrovasculature. More work is needed to understand the mechanisms underlying the cerebrovascular consequences of chronic orthostatic hypotension.

Support or Funding Information

Natural Sciences and Engineering Research Council of Canada, Canadian Institutes of Health Research, Clinical Neurosciences Pilot Research Fund Program, Libin Cardiovascular Institute, Hotchkiss Brain Institute, Compute Canada

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Carbonic Anhydrase II Deletion Confers Salt Appetite and Elicits Adaptive Regulation of Salt and Water Transporters in the Kidney
Authors: Soleimani Manoocher , Kia Mujan Varasteh , Barone Sharon , Brooks Marybeth , Zahedi Kamyar
Published: June 2021

Background

Salt appetite, which is salt craving or salt intake in excess of physiological needs, is regulated by a number of physiological mechanisms including neuronal and hormonal pathways. Excess salt intake is a major health problem and a risk factor for many diseases, including hypertension. Few genetic factors are implicated in the pathogenesis of salt appetite.

Methods and Results

Here we demonstrate that mice with the genetic inactivation of carbonic anhydrase 2 (CAII) display significant salt appetite as judged by their preference for salted water (280 mM NaCl added to the drinking water) over regular tap water, when both options are provided (average daily salted water intake of 2.80 ml in WT and 5.2 ml in CAII KO mice, p<0.01, n=5 while daily tap water intake was 4.2 ml in WT and 2.8 ml in CAII KO mice, p<0.03, n=5). The excess salt intake was observed in the absence of any vascular volume depletion or kidney dysfunction, as judged by comparable kidney renin expression and blood creatinine and BUN concentration levels in WT and CAII KO mice, and was more profound in male mice. When only provided the salted water (280 mM salt added to the drinking water), CAII null animals showed a robust increase in daily water intake vs. WT mice (20.54 ml in KO mice vs. 11.83 ml in WT, p<0.001, n=5) as well as an increase in sodium excretion (0.192 mmol/g in CAII KO vs. 0.0716 mmol/g in WT, p<.01, n=5). The expression levels of kidney sodium and water absorbing channels ENaC and AQP‐2, determined by western blotting and northern hybridization, showed robust increases (ranging from 100 to 200%) in response to enhanced salt intake in CAII KO mice vs. wild type littermates. The AVP expression levels in pituitary gland significantly increased in CAII KO mice vs. WT littermates when receiving salted water for 10 days (p<0.05), despite their comparable expression levels at baseline conditions. We propose that CAII plays an important role in regulating salt intake and its inactivation can cause salt appetite, specifically in male animals.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effect of Fragrance Inhalation of Grapefruit Essential Oil on Blood Pressure and Baroreflex Sensitivity in Human with, and without, Family History of Hypertension
Authors: Kawai Eriko , Takeda Ryosuke , Saho Kosuke , Ota Akemi , Morita Emiko , Imai Daiki , Suzuki Yuta , Yokoyama Hisayo , Okazaki Kazunobu
Published: June 2021

Purpose

Fragrance inhalation of essential oils used in aromatherapy can affect blood pressure (BP) and autonomic nervous system in humans. Considerably wide individual variations have been observed in the response, but the background factors behind the wide individual variations remain unknown. Previous studies have reported that resting circulatory variables and baroreflex sensitivity, and also the response of BP and muscle sympathetic nerve activity with mental stress and upright tilting are different between subjects with and without family history of hypertension (FH). We tested the hypothesis that the response of BP with fragrance inhalation of grapefruit essential oil (GF) was different between subjects with (FH+) and without FH (FH−).

Methods

Eighteen healthy subjects participated in this study (FH+, n = 8; FH−, n = 10). While subjects in the supine position, they breathed blank air through a face mask for 10 min as baseline (BL). Then, they inhaled air with the fragrance of GF from Douglas bags for 10 min. Beat‐by‐beat heart rate and BP were recorded continuously. Cardiovagal baroreflex sensitivity was determined with data for the last 2 min of each stage, as the slope of the liner regression between beat‐by‐beat changes in systolic BP and R‐R interval.

Results

At 6 to 10 min of BL, heart rate, systolic and diastolic BP was not significantly different between FH+ group and FH− group. During GF inhalation, diastolic BP in FH− group increased significantly (p < 0.05) from BL whereas it remained unchanged in FH+ group. Systolic BP and heart rate remained unchanged during GF inhalation in both groups. There were no significant changes in baroreflex sensitivity with fragrance inhalation in both groups.

Conclusions

The FH is a possible background factor behind the individual variation observed in the response of BP with fragrance inhalation of GF.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Physical Performance in Different Stages of Hypertension in Spontaneously Hypertensive Rats
Authors: Campos Helton Oliveira , Drummond Lucas Rios , Rodrigues Quezia Teixeira , Horta Nayara Abreu , Primola‐Gomes Thales Nicolau , Coimbra Candido Celso
Published: June 2021

The aim of study was to investigate the aerobic running performance of hypertensive rats in exercise capacity test at different ages and stages of hypertension. Male spontaneously hypertensive rat (SHR, n = 10) and normotensive wistar rats (NWR, n = 10) of 5, 8, 12 and 16 weeks were used. Experimental procedures were approved by the CEUA‐UFMG (#49/2015). Systolic blood pressure (SBP) and body mass was measured in 4 different ages. All animals were submitted to the exercise capacity test: initial speed was set to 10 m.min−1, with increments of 1 m.min−1 every 3 min until fatigue and the inclination of treadmill was maintained at 5°. The exercise time was measured and the workload was calculated as follows: body weight (kg) x exercise time (min) x treadmill speed (m.min−1) x sinα (treadmill inclination) x acceleration of gravity. The hypertensive rats had lower body mass in comparison to normotensive animals at all four ages (NWR‐5: 175 ± 5 g vs. SHR‐5:119 ± 3 g; NWR‐8: 321 ± 9 g vs. SHR‐8: 233 ± 4 g; NWR‐12: 368 ± 13 g vs. SHR‐12: 264 ± 7 g; NWR‐16: 391 ± 13 g vs. SHR‐16: 324 ± 5 g; p < 0.05, two‐way ANOVA). As expected, the SHR group presented higher SBP when compared to the NWR group at all four ages (NWR‐5: 98.7 ± 3.5 mmHg vs. SHR‐5:128.8 ± 2.6 mmHg; NWR‐8: 108.1 ± 5.4 mmHg vs. SHR‐8: 169.2 ± 3.3 mmHg; NWR‐12: 112.2 ± 2.0 mmHg vs. SHR‐12: 176.5 ± 2.0 mmHg; NWR‐16: 119.8 ± 3.3 mmHg vs. SHR‐16: 195.1 ± 7.3 mmHg; p < 0.05, two‐way ANOVA). When analyzing the physical performance measured only in the exercise time, it can be observed that all the groups showed similar physical performance in all the four moments (NWR‐5: 50.6 ± 4.1 min vs. SHR‐5: 49.6 ± 2.0 min; NWR‐8: 50.0 ± 2.5 min vs. SHR‐8: 46.8 ± 2.2 min; NWR‐12: 49.8 ± 4.2 min vs. SHR‐12: 44.8 ± 1.6 min; NWR‐16: 34.5 ± 2.1 min vs. SHR‐16: 35.2 ± 1.4 min; p > 0.05, two‐way ANOVA). However, when analyzing physical running capacity was measured by workload, it can be observed that the hypertensive animals showed a lower physical performance in comparison to normotensive animals at all four ages (NWR‐5: 140 ± 17 J vs. SHR‐5: 84 ± 6 J; NWR‐8: 206 ± 18 J vs. SHR‐8: 153 ± 8 J; NWR‐12: 264 ± 29 J vs. SHR‐12: 170 ± 9 J; NWR‐16: 195 ± 13 J vs. SHR‐16: 154 ± 9 J; p < 0.05, two‐way ANOVA). In conclusion, the present results indicate that hypertensive rats exhibit reduced physical performance compared to normotensive controls, since, the most reliable index to assess physical performance when there is difference in body mass between strains is workload.

Support or Funding Information

FAPEMIG, CAPES and CNPq

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Physiologic parameters and energetic costs of sailing specifics actions during racingcruising
Authors: Duvallet Alain Louis , Duvallet Emilie , Lhuissier François , Beaudry Michele
Published: June 2021

We determined the energetic cost of sailing skills during racing‐cruising.

The measurements are taken during four situations for two navigators practicing sailing regularly as professionals: hoist the mainsail, take reef and remove the one and go down lowering the jib sail.

The values obtained during sailing skills were compared to the oxygen consumption during a treadmill test; and the gesture being done mostly by the arms, the VO2 was measured during a triangular test with an ergometer on the arm.

The maximal oxygen consumptions are respectively on the treadmill and the arm ergometer for subject 1: 4.6 versus 4.2 l*min‐1 (91%) and for subject 2: 3.8 versus 3.5 l*min‐1 (92%). The arm VO2 is lower than the VO2max obtained on the treadmill. The arm work even at its maximum doesn't permit to express the whole oxygen utilization for both subjects.

The gestures are realized on a racing‐cruising trimaran. The measures are made by indirect calorimetry, using a portable device (Cosmed) to measure the respiratory parameters.

The duration of each skill permits to define these activities as endurance exercises (hoist the mainsail: 16 minutes, reefing: 6 minutes 30 seconds and 7 minutes, take and remove a ris: 4 minutes 45 seconds and 6 min, lower the jib sail: 5min30). During each gesture, a stable state was reached for the physiological parameters (VO2, VE, QR and FC). Different measures were taken (from 9 to 55) during this plateau allowing the calculation of average values.

The VO2 mean (± standard deviation) are for hoist the mainsail 2.4 ±0.3 l*min‐1 (62.4% of the VO2max and 67.5% of the VO2arm), for take a ris 1.9 ± 0.25 l*min‐1 (41.6% and 45.6% respectively for subject 1 and 54.4% and 59.8% for subject 2), to remove the one 2.47 ± 0.11 l*min‐1 (54% and 59% for the subject 1 and 65.5 and 70.7 for subject 2) and for lower the jib sail 1.5 ± 0.1 l*min‐1 (38.9% and 43% respectively).

The sailing specifics actions skills for racing‐cruising are endurance exercises realized by arm workouts.

The training for contestants in this field has to be oriented toward these exercises looking to improve the VO2max during arm workout. That kind of training will permit to improve the quality of the gestures during competitions, with a decrease of the exhaustion and improvement of recovery.

The values found can have their place in the compendium which lists human energy expenditure.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Dexamethasone‐Induced Effects on Autonomic Balance, Arterial Stiffness and Cardiac Remodeling in Sedentary and Trained Spontaneously Hypertensive Rats
Authors: Amaral Sandra Lia , Duchatsch Francine , Tardelli Lidieli P , Herrera Naiara A , Ruiz Thalles F.R. , Dionísio Thiago J , Santos Carlos F , Okoshi Katashi , Vicentini Carlos A
Published: June 2021

Dexamethasone (DEX)‐induced hypertension (HT) is associated with autonomic unbalance, increased arterial stiffness, reduced baroreflex gain and cardiac remodeling. Since hypertensive individuals may undergo DEX clinical treatment, it is reasonable to think that DEX treatment would exacerbate their arterial pressure, which, in turn, could culminate in a drastic increase on morbi‐mortality risk. Inversely, aerobic (AT) or combined (CT) training have been recommended for HT treatment and we have previously shown the preventive role of exercise training in counteracting DEX‐induced HT. Since nothing is known about the effects of DEX treatment in hypertensive rats, the aim of this study was to investigate if aerobic or combined training, performed before DEX treatment, would modulate autonomic balance, arterial stiffness and cardiac remodeling in spontaneously hypertensive rats (SHR) treated with DEX. Two groups of SHR (200g) underwent aerobic (AT) or combined (CT) training (60% of maximal capacity) for 8 weeks or were kept sedentary and then were treated with DEX (50μg /kg per day, s.c.) or saline (14 days). Wistar rats were used as normotensive control. Transthoracic echocardiogram and pulse wave velocity (PWV) were performed at the end of the protocol. Then, all rats underwent carotid artery catheterization for arterial pressure (AP) measurement and spectral analysis. Left ventricule (LV) was collected, weighed, and used for morphometric analysis. SHR had higher AP, PWV, LV weight, LV mass index (LVMI) and reduced systolic and diastolic function compared with wistar rats. DEX treatment (SD) did not aggravate mean AP (176±11 vs 184±8 mmHg) vs sed SHR (SC), but increased PWV (+17%). In addition, DEX did not alter the ratio between low frequency and high frequency bands of spectral analysis. DEX treatment increased LV diastolic diameter (LVDD/bw,+14%) compared with SC, but significantly decreased isovolumetric relaxation time IVRT (ms, −11%) and collagen density (−21%). Trained groups presented lower values of MAP (−18% and −13%, for AT and CT, respectively, vs SD). PWV was attenuated only by CT (−17%). Autonomic balance was not improved by training in SHR. Improved diastolic function and % of collagen (p<0.06) were observed in TD group only after AT. In conclusion, DEX treatment did not aggravate hypertension and its mechanisms in SHR, which suggests that hypertensive individuals may undergo DEX clinical treatment. Also, exercise training is a good strategy to decrease AP and improve cardiac remodeling in DEX‐treated SHR.

Support or Funding Information

Funding: FAPESP

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effect of Hypoxia on Prostate Cancer Cell Viability in Serum and Prostate Conditioned Media from Mixed‐Intensity Exercise Trained Rats
Authors: Kunkel Olivia , Opoku‐Acheampong Alexander , Baumfalk Dryden , Horn Andrew , Muller‐Delp Judy , Behnke Bradley
Published: June 2021

Background

Research suggests exercise training may alter the tumor microenvironment and facilitate conventional treatment, but the effects of exercise on prostate tumor cell growth characteristics (e.g., viability) are not well understood. In human prostate cancer cells (PC‐3), long time exposure to hypoxia decreases cellular proliferation and migration. However, whether exercise training alters tumor cell viability in hypoxia is unknown. We hypothesized that serum‐supplemented media (SSM) and prostate‐conditioned media (PCM) from mixed‐intensity exercise trained (ET) rats would decease prostate cancer cell viability versus sedentary (SED) rats in hypoxia.

Methods

Male Nrf2 rats (10–12 mo old) were randomly placed into an ET (n = 10) and a SED control (n = 4) group. The ET rats ran on a motorized treadmill for 5 days/week for 10–11 weeks. Blood serum and whole prostate were collected for preparation of SSM and PCM, respectively. PC‐3 cancer cells were grown in SSM or PCM from both rat groups for 24–96 h in a 1% O2 custom hypoxia chamber placed within a standard cell incubator. Cell viability was determined using MTT cell proliferation assay.

Results

There were no significant differences in viable cell number between SED and ET groups at 24 h (0.35 ± 0.03 vs 0.36 ± 0.02 au), 48 h (0.24 ± 0.06 vs 0.29 ± 0.04 au), and 96 h (0.47 ± 0.07 vs 0.52 ± 0.04 au) incubation in PCM. No differences were observed between the SED and ET groups at any time frame when the cells were incubated in SSM.

Conclusion

Our data does not support an effect of exercise training on cell viability in vitro with exposure to hypoxia. It remains to be determined if the growth supporting environment of the prostate or blood serum are altered with exercise training in vivo.

Support or Funding Information

American Cancer Society (RSG‐14‐150‐01‐CCE)

NIH (1 R15 HL137156‐01A1)

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.