bluuebunny/crossref_metadata_2025 huggingface dataset:
Samchulkunbitang regulates blood pressure and renal function in L‐NAME‐induced hypertensive rat
Authors: Hong Mi Hyeon , Kim Hye Yoom , Ahn You Mee , Na Se Won , Yoon Jung Joo , Lee Yun Jung , Kang Dae Gill , Lee Ho Sub
Published: June 2021

Hypertension is a risk factor for cardiovascular diseases and endothelial dysfunction was found in humans as well as in various animal experimental models of arterial hypertension. Samchulkunbitang (SCT) is Korean traditional medicine. Traditionally, the SCT was used in gastritis, gastric ulcers, and gastroptosis. This study was performed to evaluate the effect of SCT on vascular dysfunction in NG‐nitro‐L‐arginine methyl ester (L‐NAME)‐induced hypertension model. Sprague Dawley rats were divided into 5 groups; Control group, L‐NAME induced hypertension group (40 mg/kg/day), L‐NAME with olmetec (10 mg/kg/day), L‐NAME with SCT (100 or 200 mg/kg/day). L‐NAME was treated as drinking water for 3 weeks to induce hypertension in rats. Simultaneously treated L‐NAME, SCT was injected to rats by oral intake for 2 weeks. The systolic blood pressure was decreased in SCT treated groups compared with L‐NAME induced hypertension group. SCT restored vasorelaxation of response to acetylcholine, cGMP production in thoracic aorta. SCT decreased intima‐media thickness and maintained smooth and soft intimal endothelial layers in aorta of L‐NAME induced hypertension rats. SCT restored the reduction eNOS expression and decreased ET‐1 expression. Also, in western blot, SCT increased p‐eNOS and p‐Akt expression in aorta of L‐NAME hypertensive rat. Furthermore, in renal functional parameters, SCT has recovered osmolality, blood urea nitrogen (BUN), and serum creatinine level.

Taken together, these results showed that recovering relaxation and cGMP production in thoracic aorta by treated SCT, which is associated with NO/cGMP pathway. In addition, SCT suppresses increase of blood pressure in the L‐NAME induced hypertensive model as well as ameliorates in renal function.

Support or Funding Information

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 active lifestyle on heart rate variability and oxidative stress markers in offspring of hypertensives
Authors: SANTA ROSA Fernando Alves , SHIMOJO Guilherme Lemos , DIAS Danielle Silva , VIANA Ariane , LANZA Fernanda Cordoba , IRIGOYEN Maria‐Claudia , MESQUITA‐FERRARI Raquel Agnelli , DE ANGELIS Kátia
Published: June 2021

Familial history of hypertension is associated with autonomic dysfunction and increase in blood pressure (BP). On the other hand, an active lifestyle has been found to improve a number of health outcomes and reduce all‐cause mortality. The aim of the present study was to investigate the effects of an active lifestyle on hemodynamics, heart rate variability (HRV) and oxidative stress markers in offspring of hypertensive parents. One hundred twenty‐seven subjects were assigned into four groups: sedentary offspring of normotensives (S‐ON) or hypertensives (S‐OH); and physically active offspring of normotensives (A‐ON) or hypertensives (A‐OH). The level of physical activity was determined using the International Physical Activity Questionnaire. Heart rate (HR), systolic (SBP) and diastolic BP (DBP) were measured at rest. The assessment of cardiac autonomic modulation was performed by HRV analysis. Oxidant stress was assessed by Hydrogen peroxide concentration, Superoxide anion, Lipid Peroxide levels and Protein Carbonyls measurements in plasma. Diastolic BP and heart rate were reduced in the physically active groups when compared to S‐OH group. A‐ON and A‐OH groups presented increased values of RR total variance when compared to the sedentary ones (A‐ON: 4912±538 vs. S‐ON: 2354±159; A‐OH: 3112±236 vs. S‐OH: 2232±241ms2). Cardiac sympato‐vagal balance (LF/HF), systemic hydrogen peroxide and superoxide anion were markedly increased in S‐OH group when compared to all other studied groups. Systemically, superoxide anion and hydrogen peroxide were increased in S‐OH group when compared to S‐ON group. However, both physically active groups (A‐ON and A‐OH) presented reduced levels of superoxide anion (A‐ON: 41.0±4.1 and A‐OH: 48.3±3.4 vs. S‐OH: 56.7±3.9 nmol/mg of protein) and hydrogen peroxide (A‐ON: 8.95±0.9 and A‐OH: 9.6±1.8 vs. S‐OH: 16.68±2.7 μM) when compared to S‐OH group. Additionally, correlations were observed between LF/HF with diastolic BP (r=0.30, p<0.05) and hydrogen peroxide (r=0.41, p<0.05). Thus, our findings confirm the presence of early autonomic dysfunction in offspring of hypertensive parents, which was associated with a systemic increase in reactive oxygen species and blood pressure. However, our most important finding lies in the attenuation of such disorders in offspring of physically active hypertensives, thus emphasizing the importance of a physically active lifestyle in the prevention of early disorders that may be associated with development of hypertension.

Support or Funding Information

Financial support: UNINOVE, CNPq, CAPES, 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.
Plasma ATP increase is a biomarker of hypertension and triggers low‐grade inflammation through P2X7 receptor
Authors: Shen Xiao (Gregory) , Zhao Tuantuan , Shi Peng
Published: June 2021

Hypertension is accompanied with systemic low‐grade inflammation, and recent evidence shows that inflammation is a driving force of the pathogenesis of hypertension. However, what triggers inflammation in hypertension is unclear. Given that hypertension has sterile inflammation, we examined a panel of danger/damage‐associated molecular patterns (DAMPs) in the blood plasma of mice induced to hypertension by treatment of angiotensin II, L‐NAME or DOCA‐salt. We found that ATP levels consistently rose soon after the onset of hypertension and eventually reached 3 μM. ATP release upregulated CD86 expression in antigen presenting cells (APCs) and heightened immune responses in hypertensive mice. Pharmacological blockade of P2X7 receptor or genetic depletion of P2X7 expression completely abrogated CD86 upregulation, the exaggerated immune responses and blood pressure further increase in hypertensive mice. Unlike the low affinity of ATP to P2X7 in other cells, 3 μM ATP is sufficient to cause Ca2+ inflow in APCs and this is possibly due to their high contents of intracellular lysophospholipids. However, unlike 500 μM ATP, 3 μM ATP did not induce activation of inflammasome, secondary permeability pathway, or cell death in APCs, which indicates that this activation of P2X7 is at low grade. In human, untreated hypertensive patients have substantially elevated plasma ATP levels compared to treated hypertensive patients or normotensive controls. Thus, elevated ATP is a trigger of inflammation and is pathologic in hypertensive disease.

Support or Funding Information

National Natural Science Foundation of China (81670378, 81700365 and 31771266)

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Adiponectin Attenuates Cyclophilin A Induced Vascular Remodeling in Response to Mechanical Stretch and Angiotensin‐II
Authors: Radwan Zeina , Ghantous Crystal M. , Farhat Rima , Zeidan Asad
Published: June 2021

Background and aims

The mechanisms that contribute to the development of hypertension leading to cardiovascular diseases (CVD) have not been fully‐elucidated. Increased vascular pressure is associated with the formation of reactive oxygen species (ROS) in vascular smooth muscle cells. ROS has been related to the secretion of Cyclophlin A (CyPA). Moreover, studies have shown the incorporation of CyPA in CVD. Obesity is associated with decrease in adiponectin (APN) levels. Several studies have revealed that APN preserves the normal physiology of the heart. In this study, we aimed to investigate whether hypertension/mechanical stretch enhances the overexpression of CyPA protein and to explore the molecular mechanisms that mediates stretch‐induced CyPA expression. We will also assess the different possible pathways of CyPA induced vascular remodeling. We will focus on the protective effects of APN and its effects on CyPA protein expression.

Methods

Rat portal veins (RPV) organ culture with or without stretching along with aorta organ culture with or without angiotensin‐II (Ang‐II) were performed to study CyPA protein expression. CyPA treatment was also done on aorta and RPV. Western blot was used to study the expression of various proteins. Immunohistochemistry was performed to study ROS, CyPA, adiponectin and leptin expressions.

Results

This study has shown that CyPA expression increases in response to stretch in RPV and Ang‐II in aorta. Moreover, CyPA was able to increase extracellular signal‐regulated kinases 1/2 (ERK1/2) activation and to decrease 5′‐AMP‐activated protein kinase (AMPK) and endothelial nitric oxide synthase (e‐NOS) phosphorylation. CyPA was also able to increase ROS and leptin expression and to attenuate APN expression. Furthermore, we have shown that APN decreases CyPA expression. This study also demonstrated that RhoA/ROCK inhibition with Y‐27632 and ROS inhibition with apocynin inhibits CyPA expression.

Conclusion

Based on the obtained results, we showed that mechanical stretch and Ang‐II upregulates CyPA protein expression via activation of ROS and RhoA/ROCK pathway. We also demonstrated that CyPA induces vascular remodeling by phosphorylation/activation of ERK 1/2, by inhibition of AMPK and e‐NOS phosphorylation, by activation of leptin and downregulation of adiponectin. Moreover, the protective effect of adiponectin was also studied and we demonstrated that APN anti‐hypertrophic effect was in part due to inhibition of CyPA activity.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Mas1 Receptor Knockout Rats as a Novel Model to Study Vascular Function in Salt‐Sensitive Hypertension
Authors: Terashvili Maia , Uche Nnamdi , Lombard Julian H.
Published: June 2021

Hypertension is a critical risk factor for coronary and peripheral arterial disease, stroke and heart failure. It has been shown that activation of the Mas1 receptor (Mas1R) for angiotensin (1–7) [Ang (1–7)] has potent beneficial effects to offset the impaired vascular relaxation caused by increased oxidative stress, reduced nitric oxide (NO) availability, and down regulation of antioxidant defense mechanisms that occur during salt‐induced angiotensin II (ANG II) suppression. The recent development of a Mas 1R‐knockout rat (Mas 1R KO) in the Dahl salt sensitive (SS) genetic background is a crucial development, because this genetic model will allow for more detailed studies of Mas 1R function at the whole animal, molecular, and cellular level in salt‐sensitive rats. The aim of this study was to provide initial phenotyping of vascular responses in middle cerebral arteries (MCA) of wild type (WT) and Mas1R KO rats. Mas 1R KO− and WT rats were maintained on a low salt (LS; 0.4 % NaCl) diet to evaluate endothelial function without elevated blood pressure. MCA were isolated to assess vascular function ex vivo using the endothelium‐dependent vasodilator acetylcholine (ACh), exogenously added Ang (1–7), the non‐peptide Ang‐(1–7) mimic AVE 0991, and the NO donor sodium nitroprusside (SNP). ACh induced a concentration‐dependent dilation in isolated arteries from Mas 1R WT rats but not in Mas 1R KO arteries (p<0.05). Arteries stimulated with Ang (1–7) and AVE 0991 exhibited a concentration‐dependent vasodilation in Mas 1R WT but not in Mas 1R KO rats. However, endothelium‐independent vessel relaxation by SNP was unaltered in KO vessels compared to WT controls. The vasodilator effect of Ang (1–7) and AVE 0991 were eliminated by the Ang (1–7) receptor antagonist A779 and by inhibition of NO synthase with L‐NAME. Dilation of MCA in response to the AT2 receptor agonist cGP42112A was unaltered in Mas 1R KO rats. Our results indicate that Mas 1R activation has an important role in maintaining endothelial cell function in WT rats. Use of the novel Mas 1R KO genetic rat model provides a powerful tool to investigate Mas 1R functions at the molecular and cellular level. Further study of the mechanisms by which Mas1 receptors induce protective effects in the endothelium will be important since Mas 1R receptor analogs such as AVE 0991 and Ang (1–7) may offer a potentially novel therapeutic strategy for the management of hypertension.

Support or Funding Information

This work was supported in part by grants: R21‐OD024781‐01, R01‐HL128242 and T32‐GM089586 from the National Institutes of Health, Bethesda, MD

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The PDE9A inhibitor PF04447943 improves coronary arteriole vasodilation and left ventricular diastolic dysfunction in HFpEF
Authors: Bagi Zsolt , Weissman Amanda , Davila Alec , Balogh Marta , Tian Yanna , Czikora Istvan , Hamdani Nazha
Published: June 2021

Coronary microvascular dysfunction develops in patients with heart failure with preserved ejection fraction (HFpEF, also known as diastolic heart failure). Phosphodiesterase 9A (PDE9A) was shown to be upregulated in the hypertrophic myocardium in HFpEF patients. The hypothesis tested was that PDE9A inhibition improves coronary arteriole vasodilation and left ventricle (LV) diastolic function in HFpEF. The obese ZSF1 rat, a model of human HFpEF, was employed in which it was found that LV diastolic dysfunction develops by 20 weeks of age. 18‐week old male obese ZSF‐1 rats were treated with PDE9A inhibitor, PF04447943 (3 mg/kg) or vehicle by daily oral gavage for 2 weeks and LV diastolic function was assessed by transthoracic echocardiography (E/A ratio and deceleration time) and vasodilation was examined in isolated and pressurized (70 mmHg) small coronary arteries (150–200 μm in diameter) using videomicroscopy. Results showed that LV relaxation and coronary artery dilations to acetylcholine (ACh) and also to the direct nitric oxide donor, sodium nitroprusside (SNP) were significantly reduced in the 20‐week old vehicle treated obese ZSF‐1 rats, when compared to lean controls. In the PDE9A inhibitor, PF04447943 treated obese ZSF1 rats both LV diastolic function and coronary artery dilations to ACh and SNP were improved significantly. Further results revealed that ex vivo exposure of coronary arteries to PF04447943 (18 nmol/l for 30 minutes) also augmented vasodilation in response to ACh and SNP in the obese ZSF‐1 rats. It was concluded that PDE9A inhibition improves LV diastolic function and increases agonist‐induced coronary arteriole dilation in an animal model of HFpEF.

Support or Funding Information

American Heart Association 17GRNT33680171, NIH F31 HL142183‐01 and NIH R01AG054651

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Oxidative stress in concurrent hypercaloric diet and caffeine consumption in Wistar rats: Possible modulatory effects of aqueous extract of curcuma longa
Authors: Azeez Odunayo I. , Adeshina Wuraola A. , Oyagbemi Ademola A. , Ajibade Temitayo O. , Omobowale Temitayo O. , Nabofa Williams E.
Published: June 2021

Obesity and its complications have become a menace, not only in the developed world, but in developing countries as a result of sedentary lifestyles, consumption of high caloric diets and lack of exercise. This has therefore increased the incidence of complications of obesity such as diabetes, hypertension and stroke. The current study was designed to evaluate the effects of high calorie diet and caffeine consumption as well as the modulatory effects of aqueous extract of Curcuma longa in the Wistar rats.

Forty‐eight 3 weeks old male Wistar rats were used for the study. The rats were divided into eight groups of six rats each. Groups A – C were given normal rat chow while groups D – H were given high calorie diet, for 14 weeks. At fourteen weeks Group B and E were administered caffeine (5 mg/kg), Group C, Curcumin extract (500 mg/kg) while Group A and D were given water only. Group F received caffeine and curcumin extract, Group G, curcumin only while Group H received vitamin C. All the treatment was carried out for 28 days, while each of them were receiving their respective normal and high calorie diets. Blood samples were collected at 2 and 4 weeks of treatment for haematology and erythrocyte osmotic fragility. Oral glucose tolerance test (OGTT) and blood pressure were also determined while liver and kidney samples were collected for determination of markers of oxidative stress.

High calorie diet caused oxidative stress in the affected animals and predisposed to insulin resistance due to failure of blood glucose to reduce during OGTT. It also caused anaemia, hypotension and decreased erythrocyte osmotic resistance. Caffeine consumption on the other hand showed beneficial effects especially in the blockage of reactive oxygen species and other free radicals, lipid peroxidation, thereby reducing oxidative stress and liver and kidney damages. Aqueous extract of Curcuma longa however did not show appreciable antioxidant potential due to its lack of phenolic compounds and flavonoids. It however contains alkaloids, tannins, curcumin and terpenoids, which may have other benefits such as anti‐inflammatory actions.

Support or Funding Information

None

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Transplantation of Pre‐adipocytes and Stem Progenitors from Brown Adipose Tissue (BAT) Stromal Vascular Fraction (SVF) Improves Glucose Metabolism of the Recipients
Authors: Dewal Revati S. , White Joseph D. , Arts Peter J. , Baer Lisa A. , Stanford Kristin I.
Published: June 2021

Brown adipose tissue (BAT) is a thermogenic tissue that can dissipate chemical energy in the form of heat and has recently emerged as a potential therapeutic target against obesity and type 2 diabetes. Previous work in our laboratory has shown that increasing the amount of BAT by transplantation greatly improves glucose homeostasis and insulin sensitivity in a mouse model. We hypothesize that specific cell types within the BAT are responsible for this effect. The cell types in BAT include mature brown adipocytes and the stromal vascular fraction (SVF), which contains various cell types including pre‐adipocytes, stem progenitor cells and immune cells. Importantly, while tissue transplantation is a viable option in rodent models, it is not easily adaptable to human application. Transplantation of cells however is a more translatable approach for human use. Here, we isolated the SVF and cultured pre‐adipocytes and stem‐progenitor cells from BAT to identify if these cell types can improve glucose homeostasis upon transplantation. Cells were isolated from Luciferase Transgenic and then differentiated by adipogenic induction and injected into the visceral cavity of recipient wild‐type C57BL/6 mice on days 0, 1, 3, 6 and 8 of differentiation. We injected low (100k) and high (1.2 million) cell numbers. Metabolic tests (including measurements of glucose tolerance and insulin sensitivity) were performed at 4 weeks post‐transplantation. We found that transplantation of pre‐adipocytes on days 3, 6 and 8 of differentiation improve glucose tolerance in recipient mice (40.5% improvement [day 3], 10.34% improvement [day 6] and 26.32% improvement [day 8] in glucose tolerance test area under the curve (AUC) at 4 weeks post‐transplantation). These exciting data indicate that that pre‐adipocytes and stem progenitor cells isolated from BAT SVF and differentiated into adipocytes can improve glucose metabolism upon transplantation. These data will be used to develop efficient identification and transplantation approaches for cell types from BAT SVF that improve glucose homeostasis and be an important strategy to combat obesity and type 2 diabetes.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Muscle Fiber‐type Differences in Mice Selected for Wheel Running Behavior
Authors: Thong Sylvia , Garland Theodore , Rourke Bryan
Published: June 2021

Mammalian skeletal muscle fibers contain varying amounts of myosin isoforms for slow and fast myosin heavy‐chains, (Types 1, 2A, 2X, 2B,). Muscle fibers containing different isoform profiles typically correlate with variable force, speed, and fatigue resistance. We investigated the isoform profiles of various hindlimb muscles in two lines of mice, one of which has been undergoing laboratory selection for high wheel‐running behavior for over 80 generations. We hypothesized that the selected line would typically have the most type 1 or type 2a myosin. This isoform is most often expressed in muscle with higher oxidative capacity and therefore greater fatigue resistance. We collected lower leg muscles including the quadriceps, soleus, medial and lateral gastrocnemius, and plantaris from the breeding pairs of generation 80 from replicated selected and control lines.

Some data were previously reported from generations collected over a decade ago, but many muscles were not included, and we wished to see if further changes to the isoform profiles have arisen. SDS PAGE and densitometry were used to quantify the myosin isoforms.

Preliminary analysis using densitometry shows that the leg muscles of high‐running mice had a higher concentration of type 1 myosin, or in other cases, a shift towards slower type 2 fibers (i.e. 2x to 2a). The findings were highly muscle‐specific, and indicate shifts in muscle protein expression has resulted from selection.

Our new catalog of isoform profiles will serve as a baseline for comparison of two future studies – one following the development and subsequent senescence of muscle function with aging, and the second determining the effect of exercise activity on both selected and control lines.

With the aging study we hope to identify whether activity during the lifetime is as important and genetic factors in preventing the decline of muscle performance with age. For the exercise study, we hope to determine the influence of genetics on shaping exercise performance for individuals which descend from sedentary or active lines. All of these data address long‐standing nature vs nurture debates, but also bear on human clinical muscle disease, aging, and activity.

Support or Funding Information

This research was supported by California State University, Long Beach and the National Institute of General Medical Sciences of the National Institutes of Health under Award Numbers; 8UL1GM118979‐02; 8TL4GM118980‐02; 8RL5GM118978‐02. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We would also like to thank Dr. Theodore Garland from University of California, Riverside and Dr. Angela Horner from California State University, San Bernardino.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
EXERCISE TRAINING ASSOCIATED WITH DIETARY ADJUSTMENT INDUCES METABOLIC AND CARDIOVASCULAR BENEFITS IN HIGH‐FAT‐FED MENOPAUSE RATS
Authors: dos Santos Adriano , da Costa Santos Nicolas , do Nascimento‐Carvalho Bruno , Carvalho Sabrina Leonardo , Mello‐Silva Fernanda Queiroz , Stabile Gabriel Correia , Izaías João Eduardo , Irigoyen Maria‐Claudia , De Angelis Kátia , Scapini Kátia Bilhar , Sanches Iris Callado
Published: June 2021

Introduction

Considering the increase in cardiometabolic risk after menopause, and that diet and exercise training (ET) are the pillars of prevention/treatment strategies, the objective of this study was to evaluate the metabolic, hemodynamic and autonomic effects of exercise training in an experimental model of menopausal undergoing a high‐fat diet followed by dietary adjustment. Twenty female C57BL/6J mice (8 weeks aged), all oophorectomized (bilateral ovarian removal) divided into 4 experimental groups (n = 5) were used: sedentary submitted to a high‐fat diet (OSD), sedentary submitted to 4 weeks of high‐fat diet and 4 weeks of control diet (OSRa), trained submitted to a high‐fat diet (OTD), trained submitted to 4 weeks of high‐fat diet and 4 weeks of control diet (OTRa). Oophorectomy was performed at the end of the 4th week of the protocol. Fasting glycemia and oral glucose tolerance were evaluated. ET had duration of 4 weeks (6th to 9th week of protocol, 5 days/week, 1 hour/day, intensity 50–70% of the maximum treadmill test). At the end of the protocol, the animals were cannulated for direct recording of arterial pressure (AP), after which baroreflex sensitivity and cardiovascular autonomic modulation were analyzed.

RESULTS

Dietary adjustment promoted a reduction in glycemia and a better glucose tolerance, associated with reduction in cardiac sympathetic modulation (LF‐PI: OSD: 0.54±0.02; OSRa: 0.37±0.06; OTD: 3.0±0.02, OTRa: 0.19±0.02 ms2) and vascular (LF‐SAP: OSD: 11.3±1.7, OSRa: 3.6±0.9, OTD: 1.6±0.2; OTR:3.0±0.5mmHg2). ET, with or without dietary adjustment, increased physical capacity, reduced heart rate, improved baroreflex sensitivity, increased cardiac parasympathetic modulation (HF‐PI: OSD: 0.47±0.04, OSRa: 0,63±0.07, OTD: 0.86±0.02, OTRa: 0.75±0.07 ms2) and reduction of cardiac and vascular sympathetic modulation. However, only the association of ET with dietary adjustment was able to promote reduction in body weight, glycemia, improvement in glucose tolerance, reduction in blood pressure (mean AP: OSD: 123±2.1, OSRa: 114±0.8; OTD: 120±1.4; OTR: 110±4.0 mmHg), and further increase in parasympathetic modulation. Thus, the association of ET with dietary adjustment may be considered an important behavior for the management of cardiovascular risk in the association of obesity with ovarian deprivation.

Support or Funding Information

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior ‐ Brazil (CAPES) ‐ Funding Code: 001.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Effects of Expiratory Muscle Strength Training on Run Performance in Healthy College Students
Authors: Bernard Jeffrey R , Thao Nou , Sanders Krystle K , Liao Yi‐Hung
Published: June 2021

Purpose

Expiratory muscle strength training (EMST) is a novel and noninvasive intervention to improve expiratory capacity. EMST programs have been shown to benefit individuals who have difficulty breathing, swallowing, and coughing by improving expiratory muscle strength. However, it is unclear if EMST can benefit those without impaired respiratory capacity. Thus, the purpose of this study was to investigate the effects of EMST on run performance in healthy college students.

Methods

This was a repeated measure study design in which participants performed body composition, maximal expiratory pressure (PEmax), VO2max, and 5K run time before and after 4‐weeks of training. In addition, blood samples were obtained immediately before and after the 5K to measure lactic acid, glucose, and epinephrine. Twenty‐one college students were recruited and matched, based on their pre‐VO2max, into 1 of 3 treatment groups (n=7 for each): 1) EMST, 2) aerobic training (AT), or 3) EMST‐AT (combined EMST and aerobic training). EMST was performed 5 d/wk starting at 75% PEmax and progressively increased the resistance throughout the 4‐weeks. AT was performed 4 d/wk for 4‐weeks by progressively increasing run volume up to 5K. EMST‐AT performed both interventions.

Results

There were no differences among treatment groups for the pre‐measurements. Body composition did not significantly change throughout the study. After 4‐weeks of training all groups improved PEmax, VO2max, and 5K run time. However, the improvement in PEmax was significantly greater for both EMST and EMST‐AT compared to AT. Although there was a trend for improved VO2max and 5K run time for AT and EMST‐AT compared to EMST, the differences were not statistically significant. There were no differences found for the blood variables among treatment groups.

Conclusion

EMST appears to provide similar benefits to that of short‐term aerobic training in healthy college students. However, the long‐term benefits of EMST compared to aerobic training warrant further investigation.

Support or Funding Information

This study was funded, in part, by a Research Scholarship and Creative Activities (RSCA) grant from California State University, Stanislaus.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Whole body exercise training improves blood pressure and postural balance responses during orthostatic stress onset in older women
Authors: Ferreira Luana Farinazzo , Rodrigues Gabriel Dias , Soares Pedro Paulo Silva
Published: June 2021

The purpose of the current study was to investigate the effects of whole body exercise training on spontaneous baroreflex sensitivity at rest, blood pressure and postural balance responses during orthostatic onset in older women. The sample composed by eight healthy older women (65±3 yrs.). R‐R intervals and blood pressure were continuously measured from a standard electrocardiogram (ECG) and infrared finger plethysmography, respectively, at rest (10min) and during orthostatic position (7min). Spontaneous baroreflex sensitivity at rest was obtained by spectral method in the low‐frequency component of R‐R and systolic blood pressure time series (αLF). The nadir point was considered the lower value of mean arterial pressure (MAP) during transition from supine to orthostatic position. The percentage changes (%ΔMAP) from supine to orthostatic nadir were calculated. The time of MAP oscillations during orthostatic onset (MAPtime) was calculated by the sum of time to nadir and time to recovery (nearest value of MAP at rest). In addition, during the ORT onset (15s) the center of pressure displacements (COP) were acquired by a force plate, and COP distance and speed were calculated. The whole body exercise training protocol (rowing ergometer) consisted of three weekly sessions (30 minutes) at 60–80% of maximal heart rate (defined by a previous maximal exercise test) for 10 weeks. The volunteers were evaluated pre and post‐trainning. Student‐t tests for paired samples was employed (p≤0.05) to compare all variables. At rest, αLF (pre= 3.9 ±1.7 vs. post= 5.3 ±1.1 ms2 p<0.001) increased post‐training and MAP (pre= 85.1 ±10.3 vs. post= 77.4 ±7.8 mmHg p< 0.02) decreased. No differences in CO (pre= 4.526 ±0.7697 vs. post= 5.058 ±2.104 L/min p=0.02) and SV (pre= 66.33 ±19.94 vs. post= 72.18 ±29.67 mL p=0.01) were found at rest. Although %ΔMAP (pre= −0.3 ±0.2 vs. post= −0.3 ±0.16 mmHg p< 0.19) was not different pre and post training, MAPtime (pre= 14.16 ±3.996 vs. post= 10.94 ±5.637 seconds p<0.04) decreased post‐training protocol. Moreover. COP distance (pre= 673.7 ±74.9 vs. post= 560.3 ±95.1 mm p< 0.03) and speed (pre= 44.9 ±4.9 vs. post= 37.3 ±6.3 mm/s p<0.03) were lower post‐training. Whole body exercise training improves spontaneous baroreflex sensitivity at rest mean arterial pressure and postural balance adjustments during orthostatic stress onset in older women. Research ethics committee (CEP‐851.371/14).

Support or Funding Information

Foundation for Research Support of the State of Rio de Janeiro ‐ FAPERJ (E‐6/110.079/2013), Coordination for the Improvement of Higher Education Personnel ‐ CAPES.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Neurovascular Coupling is Blunted in Atrial Fibrillation
Authors: Junejo Rehan T. , Phillips Aaron , Lucas Samuel J. E. , van Lieshout Johannes J. , Lip Gregory Y. H. , Fisher James P.
Published: June 2021

People with atrial fibrillation are at an increased risk of stroke, cognitive decline and dementia. We recently identified that individuals with atrial fibrillation exhibit a reduced cerebrovascular reactivity to carbon dioxide, indicative of a diminished cerebral vasodilatory reserve. In this study we sought to determine whether neurovascular coupling (NVC) is blunted in atrial fibrillation in comparison with age‐matched, hypertensive and healthy control participants.

Posterior (PCA) and middle cerebral artery (MCA) flow velocity (Vm), along with beat‐to‐beat mean arterial pressure (MAP), were measured during a NVC assessment consisting of five cycles of visual stimulation (reading) for 30 s followed by 30 s with both eyes‐closed in 12 patients with atrial fibrillation (69 [7] yr; mean [SD], 3 women), 13 patients with hypertension (67 [5] yr, 4 women) and 12 healthy control participants (63 [10] yr, 4 women). Cerebrovascular conductance indices (CVCi) were calculated as PCA Vm/MAP and MCA Vm/MAP. NVC was denoted by the peak response observed during visual stimulation and is expressed as a percentage change from the eyes‐closed period.

Resting PCA Vm and MCA Vm were not different between the atrial fibrillation (31 [7] and 49 [12] cm/s), hypertension (33 [8] and 55 [12] cm/s), and healthy control (36 [8] and 55 [12] cm/s) groups (P>0.05). Visual stimulation evoked an increase in PCA CVCi in all groups, but the magnitude of the hyperemic response was blunted in patients with atrial fibrillation (18 [8] %) and hypertension (17 [8] %), in comparison with healthy controls (26 [9] %) (P<0.05). Visual stimulation evoked a greater increase in MCA CVCi in the atrial fibrillation group (17 [6] %), than patients with hypertension (10 [4] %) and healthy controls (13 [6] %) (P<0.05). Thus, when peak PCA CVCi responses were considered following subtraction of the peak MCA CVCi responses (i.e., the “non‐selective” effect of the NVC test), a significantly diminished response was observed in the atrial fibrillation group (1 [8] %) compared the hypertension (7 [9] %) and healthy control groups (13 [9] %) (P<0.01).

In summary, individuals with atrial fibrillation exhibit a blunted NVC response to visual stimulation when compared to age‐matched, healthy control and hypertensive participants. Additional studies are required to identify the mechanisms for the attenuated cerebral perfusion response of the occipital lobe to visual stimulation in atrial fibrillation (e.g., attenuated neuronal activation, altered cerebrovascular vasodilatory signaling).

Support or Funding Information

Funded by BHF project grant PG/15/45/31579.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Compromised endothelial function in transgender men taking testosterone
Authors: Stachenfeld Nina , Leone Cheryl , Gulanski Barbara
Published: June 2021

Approximately 0.6% or 1.4 million people identify as transgender or having a current gender identity that differs from the sex assigned at birth. Transgender men (TGM) are persons assigned female at birth with a male gender identity. In TGM, testosterone therapy may be associated with increased blood pressure (BP), lipids, triglycerides, LDL cholesterol and decreased HDL‐cholesterol. Androgen excess is a major driver of endothelial dysfunction among cisgender females (CGF), and endothelial dysfunction is an early sign of atherosclerosis and hypertension. We therefore examined endothelial function in TGM receiving testosterone. We hypothesized that endothelial function in TGM would be attenuated compared to CGF of similar age and BMI. We compared 4 TGM (age 26 ± 5 y; BMI 26.3 ± 3.2 kg/m2) receiving testosterone (T) to 8 CGF (25 ± 4 y; BMI 25.7 ± 6.8 kg/m2) during the early follicular phase of their menstrual cycle. We evaluated brachial vasodilatory responses following stimuli designed to elicit shear stress using 5‐min occlusion to determine endothelial function (flow mediated vasodilation, FMD). As expected, total T was increased in the TGM compared to CGF (457.4 ± 119.8 vs. 1.9 ± 1.1 ng/dL), as was free T (72. ± 7.5 vs. 1.5 ± 0.9 pg/dL). Blood lipids, including LDL (98.6 ± 38.5 mg/dL), HDL (51.5 ± 11.1 mg/dL) and triglycerides (79.0 ± 31.9 mg/dL) as well as HbA1c (4.9 ± 0.1%) were within normal ranges in the TGM. Systolic BP (SBP) was elevated in 2/4 TGM and 3/8 CGF; MAP was similar between groups (90 ± 21 and 90 ± 10 mm Hg). However, FMD was attenuated in the TGM (3.7 ± 3.5 %) compared to the CGF (9.2 ± 1.2 %, P=0.001) indicating markedly diminished endothelial function in TGM receiving androgen treatment. Further, endothelial dysfunction was independent of other risk factors associated with cardiovascular disease including hyperlipidemia, diabetes and hypertension. In transgender men, the androgen‐dominant hormonal milieu appears to impair endothelial function. Endothelial dysfunction precedes clinically detectable atherosclerotic plaques in the coronary arteries and is an important marker for cardiovascular risk. Therefore, attention to cardiovascular risk factors should be integral to the care of transgender men.

Support or Funding Information

R01 HL135089

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 iNOS on Cutaneous Thermal Hyperemia in Non‐Hispanic Blacks versus Non‐Hispanic Whites
Authors: Miller James , Hollowed Casey , Otis Jeff , Hayat Matthew , Quyyumi Arshed , Wong Brett
Published: June 2021

Non‐Hispanic Blacks exhibit a blunted cutaneous microvascular response to local heating due, in part, to a decrease in nitric oxide (NO) bioavailability compared to non‐Hispanic Whites. Inducible NO synthase (iNOS) is known to contribute to vascular dysfunction; however, it is unknown whether iNOS contributes to microvascular dysfunction in NHB. The purpose of this study was to examine the role of iNOS on cutaneous microvascular function in NHB vs. NHW. Young, healthy non‐Hispanic Black and White participants (n = 4 per group) were instrumented with 2 microdialysis fibers for infusion of lactated Ringer's solution (control) and 0.1 mM 1400W (iNOS inhibitor), respectively. Following Ringer's and 1400W infusion, local skin temperature was increased via rapid local heating to 39°C at a rate of 0.1°C s−1. Once skin blood flow plateaued, 20 mM L‐NAME was infused to quantify endothelial NO synthase (eNOS)‐dependent vasodilation to the local heating response. Following L‐NAME infusion, the local heaters were increased to 43°C and 54mM of sodium nitroprusside was infused to elicit maximal endothelium‐independent cutaneous vasodilation. Skin blood flow was measured via laser‐doppler flowmetry (LDF) throughout the local heating protocol. Cutaneous vascular conductance (CVC) was calculated as LDF flow divided by mean arterial pressure and normalized to maximum (%CVCmax). iNOS inhibition minimally increased the initial peak in non‐Hispanic Blacks (33±6 vs. 41±8 %CVCmax) but had no effect in non‐Hispanic Whites (53±9 vs. 55±6 %CVCmax), suggesting an increased sensory nerve response in non‐Hispanic Blacks following blockade. Inhibition of iNOS (66±10 %CVCmax) did not alter microvascular function compared to control (70±14 %CVCmax) in non‐Hispanic Whites; however, microvascular function increased (47±11 vs. 60±10 %CVCmax) in non‐Hispanic Blacks, suggesting an increase in basal iNOS concentrations. Notably, iNOS inhibition in non‐Hispanic Blacks increased %CVCmax to a level similar to non‐Hispanic Whites. The %NO‐dependent vasodilation did not change in non‐Hispanic Whites with infusion of 1400W (60±5 vs. 61±5 %); however, infusion of 1400W increased the %NO‐dependent vasodilation in non‐Hispanic Blacks (44±6 vs. 57±3 %), suggesting increased levels of circulating iNOS impairs endothelial‐dependent vasodilation. These findings indicate iNOS‐derived NO contributes to reduced eNOS‐dependent microvascular vasodilation in young, healthy non‐Hispanic Blacks.

Support or Funding Information

Grant Number: 1R01HL141205‐01

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Determinants of Peak Oxygen Uptake in Patients with Chronic Obstructive Pulmonary Disease: Looking Beyond the Lungs
Authors: Broxterman Ryan M , Nelson Ashley D , Lawrenson Lesley , Poole Jennifer G , Hoff Jan , Wagner Peter D , Richardson Russell S
Published: June 2021

Peak oxygen uptake (V̇O2peak), a primary determinant of prognosis, mortality, and quality of life, is diminished in patients with chronic obstructive pulmonary disease (COPD). Of importance, even after lung function is restored, by lung transplant, V̇O2peak remains markedly attenuated, emphasizing the critical importance of peripheral dysfunction in this pathology. However, the peripheral determinants of V̇O2peak in patients with COPD remain poorly understood. Therefore, the purpose of this investigation was to assess the peripheral determinants of V̇O2peak in patients with COPD, to better understand disease‐related peripheral adaptations. Oxygen transport and utilization at peak single‐leg knee‐extensor exercise were assessed from arterial and femoral venous oxygenation measurements and leg blood flow (by thermodilution) in 8 patients with COPD (FEV1 = 0.9 ± SE 0.1 L, 30% of predicted) and 8 well‐matched control subjects. This exercise modality was utilized to minimize cardiopulmonary exercise limitations. Muscle convective O2 delivery (0.44 ± 0.06 vs. 0.69 ± 0.07 l/min, p<0.05) and muscle diffusive O2 conductance (6.6 ± 0.8 vs. 10.4 ± 0.9 ml/min/mmHg, p<0.05) were both ~1/3 lower in COPD patients than control subjects, resulting in a significantly attenuated leg V̇O2peak in the patients (0.27 ± 0.04 vs. 0.42 ± 0.05 l/min, p<0.05). Thus, in an exercise paradigm that minimizes cardiopulmonary limitations, the convective and diffusive components of oxygen transport within skeletal muscle, key determinants of V̇O2peak, are markedly diminished in patients with COPD. These findings emphasize the importance of peripheral factors, beyond the lungs, that limit exercise capacity, exacerbate inactivity, and increase the risk for cardiovascular disease in patients with COPD.

Support or Funding Information

Supported by National Heart, Lung, and Blood Institute Grant HL‐091830

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Estradiol treatment and exercise improve hepatic mitochondrial outcomes in mice following ovariectomy
Authors: Fuller Kelly N.Z. , Houchen Claire , Choi Michael , Allen Julie A. , McCoin Colin S. , Morris E. Matthew , Von Schulze Alex T. , Thyfault John P.
Published: June 2021

We recently reported that female mice have increased hepatic mitochondrial respiratory capacity, and differential responses to exercise compared to male mice. Here we sought to determine the role of estrogen in the enhanced hepatic mitochondrial function found in female mice. Female C57BL mice (n= 4–6 per group) were randomly assigned to sham surgery (Sham), ovariectomy (OVX), or OVX plus estradiol replacement therapy from ~8 to 13 weeks of age. Half of the mice in each group were assigned to sedentary (SED) or voluntary wheel running (VWR). All mice had ad libitum access to high‐fat diet (HFD). We assessed isolated hepatic mitochondrial respiratory capacity using the Oroboros O2k with both pyruvate and palmityl‐carnitine as substrates. VWR reduced basal respiratory capacity of palmityl‐carnitine across all treatment groups. The OVX+Est group displayed increased State 3 respiratory capacity with pyruvate. Interestingly, in the absence of estrogen (OVX), both VWR and exogenous estradiol treatment independently improve the coupling control ratio (Basal/State 3: representative of coupling efficiency) and leak control ratio (Basal/Uncoupled: indicative of free ETS capacity) with pyruvate. We further assessed liver whole homogenate electron transport chain (ETC) protein content and found independent and combined effects of estradiol and exercise that were complex‐specific. The OVX group had a unique compensatory effect of increased Complex I protein with VWR, that was diminished with estradiol add‐back. Further investigation of treatment effects for complexes I‐IV, suggest that statistical differences are driven by the OVX. Interestingly, the sedentary OVX+Est group presented similarly to the Sham VWR group. In conclusion, these data suggest that ovariectomy leads to reduced hepatic mitochondrial respiratory control, and that estradiol replacement and modest exercise can aid in rescuing this phenotype.

Support or Funding Information

This work was funded by VA Merit Review: 1I01BX002567‐01

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Hindlimb Denervation Alters the Regulation of Autophagy and Mitophagy
Authors: Triolo Matthew , Hood David A
Published: June 2021

During chronic muscle disuse, fibre atrophy occurs concomitantly with reductions in mitochondrial content and function. The reduction in organelle content is due, in part, to depressed mitochondrial biogenesis and elevations in intracellular degradation processes. The regulation of mitochondrial biogenesis has been studied extensively. However, the processes that underlie the degradation of mitochondria have yet to be fully elucidated. The breakdown of the organelle is due to a selective form of autophagy, termed mitophagy. When a mitochondrion becomes dysfunctional it dissociates from the mitochondrial network within the muscle and is subsequently degraded by lysosomes. The objective of this work is to better understand the processes of autophagy and mitophagy in the context of muscle disuse. Accordingly, we employed a hindlimb denervation protocol in which we unilaterally sectioned the peroneal nerve of one hindlimb, using the contralateral limb as a control in Sprague‐Dawley rats. Protein measurements of autophagy and mitochondrial content markers were made at 1, 3 and 7 days post‐denervation. We observed significant 25–30% (p<0.05) reductions in extensor digitorum longus (EDL) and tibialis anterior (TA) muscle mass by 7 days post‐denervation. Significant elevations in the autophagy proteins Tfeb, Beclin1 and ATG‐7 were also measured 7 days post denervation, while mitochondrial protein COX subunit‐IV and COX enzyme activity were reduced by 25% and 40%, respectively. However, SS and IMF mitochondrial respiratory capacity was diminished, accompanied by enhanced reactive oxygen species production, as early as 1–3 days following denervation. To investigate the early changes in autophagy and mitophagy flux that may explain the alterations in mitochondrial content and function, a subgroup of animals was treated with colchicine (4mg/kg/day) for 2 days to inhibit autophagic breakdown in response to 1 and 3 days of denervation. LC3‐II autophagy flux was increased as early as 1 and 3 days post‐denervation, but diminished by 7 days, in part as a result of a denervation‐induced increase in LC3‐II expression. Mitophagy flux was increased in parallel in SS mitochondria, and by 3 days in the IMF subfraction. These changes appeared to coincide with the declines in mitochondrial function, suggesting that although mitophagy is elevated, it is not sufficient to eliminate all of the dysfunctional organelles. Furthermore, the immediate elevations in autophagy/mitophagy flux at 1 and 3 days occurred prior to the upregulation of autophagy and lysosomal markers at 7 days post‐denervation, suggesting that the intrinsic activity of the autophagosomal breakdown pathway is sufficient in the early time course, but is subsequently upregulated to meet the demands of prolonged denervation.

Support or Funding Information

Supported by NSERC, 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.