bluuebunny/crossref_metadata_2025_split 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 InformationThis 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 InformationFinancial 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 InformationNational 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 aimsThe 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.MethodsRat 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.ResultsThis 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.ConclusionBased 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 InformationThis work was supported in part by grants: R21‐OD024781‐01, R01‐HL128242 and T32‐GM089586 from the National Institutes of Health, Bethesda, MDThis 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 InformationAmerican Heart Association 17GRNT33680171, NIH F31 HL142183‐01 and NIH R01AG054651This 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 InformationNoneThis 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 InformationThis 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.