bluuebunny/crossref_metadata_2025_split huggingface dataset:
Angiotensin‐(1‐7) Attenuates Blood Pressure and Cardiac Hypertrophy in Aged Mice
Authors: Miller Amanda J. , Bingaman Sarah S. , White Melissa , Arnold Amy C. 
Published: June 2021

BackgroundAging is associated with an increase in blood pressure, which is attributed to multiple factors including endothelial dysfunction, cardiac hypertrophy, and changes in cardiovascular autonomic regulation including increased sympathetic tone and reduced measures of parasympathetic tone. In addition, altered responsiveness of the renin‐angiotensin hormone angiotensin (Ang) II has been implicated in age‐related cardiovascular risk. The deleterious actions of Ang II are generally opposed by the vasodilatory and cardioprotective hormone Ang‐(1‐7); however, to our knowledge no studies have evaluated the importance of Ang‐(1‐7) to blood pressure regulation during aging. In this study, we hypothesized that Ang‐(1‐7) would improve blood pressure and cardiac autonomic control in healthy aged mice.MethodsSixteen month‐old male C57BL/6J mice received 6‐week Ang‐(1‐7) [400 ng/kg/min, n=5] or saline infusion (n=3) via subcutaneous osmotic mini‐pumps. All mice were fed standard chow diet (18% kcal from fat). Blood pressure was measured during the last week of treatment via a carotid artery catheter connected to a strain‐gauge transducer and blood pressure analyzer. Cardiac sympathetic and parasympathetic tone and sympathovagal balance were calculated from the blood pressure signal using spectral analysis frequency domain methods. Heart weight and the heart: body weight ratio was determined at end of experiments.ResultsAng‐(1‐7) significantly decreased systolic [Ang‐(1‐7): 102±1 mmHg, saline: 112±6 mmHg, P=0.050] diastolic [Ang‐(1‐7): 78±2 mmHg, saline: 85±2 mmHg, P=0.033], and mean [Ang‐(1‐7): 86±2 mmHg, 94±3 mmHg, P=0.029] blood pressure in aged mice. The blood pressure‐lowering effect of Ang‐(1‐7) was associated with a trend towards reduced sympathetic tone [Ang‐(1‐7): 0.17±0.06, saline: 0.29±0.03, P=0.081], with no effect on vagal tone [Ang‐(1‐7): 0.25±0.11, saline: 0.17±0.06, P=0.625]. Furthermore, Ang‐(1‐7) reduced heart weight [Ang‐(1‐7): 0.19±0.01 g; saline: 0.23±0.02 g, P=0.044] and the heart to body weight ratio [Ang‐(1‐7): 0.004±0.001; saline: 0.006±0.001, P=0.022]. There was no effect of Ang‐(1‐7) on body weight or composition (P > 0.2).ConclusionsChronic Ang‐(1‐7) treatment lowers blood pressure and attenuates cardiac hypertrophy in aged mice, even in the absence of effects on body composition. The blood pressure‐lowering effects of Ang‐(1‐7) appear to involve a decrease in cardiac sympathetic tone; although further studies are needed to confirm these findings. These overall data suggest Ang‐(1‐7) may provide a novel pharmacological target to improve age‐related cardiovascular risk.Support or Funding InformationNIH 5 R00 HL122507‐04, American Heart Association Postdoctoral Fellowship 18POST33960087This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Endothelin B Receptors are Necessary for Appropriate Renal Afferent Nerve Responsiveness
Authors: Becker Bryan K , Kopp Ulla C , Pollock David M 
Published: June 2021

Salt‐sensitive hypertension is a major health burden with end results of increased mortality and morbidity worldwide. Many factors contribute to salt‐sensitive hypertension including endothelin (ET) system dysfunction and aberrant sympathetic nerve activity. Previous work has highlighted the involvement of the ET system in modulating sympathetic tone; however, a complete understanding of the interactions involved remains elusive. Prior studies suggest that ETB receptors sensitize renal afferent nerves in response to high salt diet, which initiates a feedback loop via the renorenal reflex to inhibit efferent renal nerve activity and thus promote natriuresis. Rats lacking functional ETB receptors in all tissues except adrenergic tissues (ETB ‐def) are hypertensive, salt‐sensitive, and have elevated sympathetic tone. We have shown that bilateral renal denervation in ETB‐def rats attenuates blood pressure along with markers of global autonomic tone suggesting a role for afferent renal nerves in mediating hypertension in this model. Here, we hypothesized that ETB ‐def rats would have attenuated afferent nerve activation compared to transgenic (TG) controls. Renal pelvic walls were collected from TG and ETB ‐def rats and treated with prostaglandin E2 (PGE2). Substance P release was measured as an indicator of the activation of afferent nerves within the isolated pelvic walls. Substance P release was significantly higher in pelvic walls following treatment with PGE2 from TG compared to ETB ‐ def male rats (9.5 ± 2.8 vs. 0.1 ± 0.5 pg/min, p < 0.01, n = 5/group, respectively) and females (8.1 ± 1.2 vs. 0.7 ± 1.0 pg/min, p < 0.05, n = 5/group, respectively). Substance P release in response to capsaicin was not different between genotypes (4.2 ± 1.3 vs. 4.6 ± 1.8 pg/min, p = 0.85, n = 6/group, TG vs. ETB ‐def) indicating intact afferent nerve responsiveness. Preliminary data further indicate that ETB‐def animals do not display reduced renal sympathetic tone following a high salt diet. Rats were fed either a normal salt diet (0.49% NaCl) or high salt diet (4% NaCl) for 7–10 days, and total renal nerve activity was measured in anesthetized rats. TG controls tended to have lower nerve activity following high salt (1.8 ± 0.3 vs. 1.1 ± 0.2 mV.ms, n = 3–4/group, normal vs. high salt). Conversely, ETB‐def rats failed to display this reduction in sympathetic tone (1.8 ± 1.0 vs. 3.2 ± 0.3 mV.ms, n = 3/group, normal vs. high salt). These data indicate that salt‐sensitive ETB ‐def rats have impaired afferent renal nerve responsiveness, which results in a lack of renorenal reflex mediated sympathoinhibition.Support or Funding InformationSupported by T32 HL007457 to BKB, and P01 HL069999 and P01 HL136267 to DMP.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 Role of the Endothelin System in the Progression of Acute Kidney Injury to Chronic Kidney Disease
Authors: Czopek Alicja , Stewart Kevin , Moorhouse Rebecca , Bailey Matthew A , Dhaun Neeraj 
Published: June 2021

IntroductionAcute kidney injury (AKI) is the most common cause of organ dysfunction in critically ill patients, increasing the risk of developing chronic kidney disease (CKD) by 30%. Endothelin‐1 (ET‐1) is the most potent endogenous vasoconstrictor mediating its effects through two receptors – the endothelin‐A receptor (ETA) and endothelin‐B receptor (ETB). The ET system is upregulated in AKI and CKD. We investigated the role of the ET system in the progression of AKI to CKD using the renal ischemia‐reperfusion injury (IRI) model.MethodsStudy 150 min of unilateral IRI was induced by occlusion of the left renal pedicle in male FVB mice. Starting 24h after injury, mice received either 4 weeks of sitaxentan (a selective ETA receptor antagonist; n=12) or vehicle (n=12) in drinking water. Blood pressure (BP) was recorded continuously over the 4‐week period via radiotelemetry and kidney fibrosis assessed at the end.Study 2Using a similar protocol, mice received either sitaxentan (n=8) or vehicle (n=8) for 5 days after which animals were anesthetized and BP measured using a carotid artery cannula, and renal cortical and medullary blood flows measured in the IRI kidney by laser Doppler flowmetry. We assessed systemic and renal hemodynamic responses to brief intravenous infusion of angiotensin II (ANG II).ResultsStudy 1Unilateral renal IRI led to a sustained increase in BP of ~8 mmHg and significant fibrosis within the IRI kidney. Sitaxentan completely prevented this BP rise and the development of fibrosis.Study 2In healthy mice, brief ANG II infusion increased systemic BP and reduced renal cortical and medullary blood flow. Unilateral renal IRI enhanced the BP rise seen with ANG II infusion and significantly attenuated the falls in renal cortical and medullary blood flow in the IRI kidney. 5 days of sitaxentan treatment improved the renal hemodynamic response to ANG II.ConclusionsWe have demonstrated that administration of a selective ETA receptor antagonist improves the perturbations in systemic and renal hemodynamic seen in a model of AKI transitioning to CKD. These may be of important therapeutic benefit and should be pursued in a clinical trial in relevant patient groups.Support or Funding InformationThis work was funded by the British Heart Foundation and the Medical Research Council.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Chronic Intermittent Hypoxia is Associated with Sustained Reduction in Renal Blood Flow and Downregulation of Renal KLF2
Authors: Twohey Stephanie C. , Kious Kiefer W. , Keomanivong Faithe E. , Neidermann Sarah E. , Dirkman Jacob J. , Marcus Noah J. 
Published: June 2021

Background and RationaleSleep apnea (SA) is associated with hypertension and chronic kidney disease. Dysregulation of blood pressure control and renal damage may occur because of the chronic intermittent hypoxia (CIH) that occurs during SA. Reductions in renal blood flow (RBF) during or after CIH may lead to renal injury by contributing to recurrent tissue hypoxia and alterations in shear‐stress (SS) related signaling. Krüppel‐like factor 2 (KLF2) is a SS‐sensitive transcription factor that controls expression of antioxidant and anti‐inflammatory gene programs.HypothesisWe hypothesized that CIH would result in baseline reductions in RBF and exacerbate subsequent reductions in RBF during hypoxia. Furthermore, renal KLF2 expression will be reduced along with attendant changes in its downstream targets.MethodsAdult male Sprague Dawley rats were exposed to 10 days CIH (60 sec. 10% O2, 120 sec. 21% O2) for 8h/d. Post‐CIH (or sham) RBF was measured using Transonic flow probes before, during, and after exposure to 10% O2. After euthanasia, renal cortical and medullary tissue was probed for expression of KLF2, interleukin 6 (IL‐6), superoxide dismutase (SOD1), neutrophil gelatinase‐associated lipocalin (NGAL) via western blot.ResultsBaseline weight‐corrected RBF was lower in CIH vs. sham (1.89±0.13 mL/min/g vs. 1.42±0.16 mL/min/g, p<0.05), and the RBF response to 10% O2 was accentuated in CIH vs. sham (−45±14% CIH vs. −26±4% sham, p<0.05). During recovery, RBF at 20 min post‐hypoxia remained below baseline values in both groups (93±3% of baseline sham vs. 85±4% of baseline CIH, P>0.05). Ten consecutive episodes of 10% O2 elicited reductions in RBF that persisted after return to 21% oxygen and which were significantly reduced from baseline for the duration of the exposure period (p<0.05). Cortical and medullary KLF2 expression were decreased by 40–50% in CIH relative to sham (1.00±0.21 sham cortex vs. 0.46±0.08 CIH cortex, and 1.00±0.24 sham medulla vs. 0.44±0.10 CIH medulla, p<0.05 for both comparisons). Cortical SOD1 expression was reduced in CIH relative to sham (1.00±0.00 sham vs. 0.72±0.12 CIH, p<0.05), whereas IL‐6 expression was increased (1.00±0.19 sham vs. 1.56±0.21 CIH cortex, p<0.05). Medullary NGAL was increased in CIH vs. sham (p<0.05).ConclusionPersistent reductions in RBF during and after apneic episodes (CIH) may contribute to renal inflammation, oxidative stress, and injury via downregulation of KLF2.Support or Funding InformationSupported by a grant from NHLBI (R15 HL138600‐01 to NJM)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Involvement of AKT/FOXO Genes in the Interactions of PPARα and PHD in DOCA‐Induced Pathology
Authors: CHOI MYUNG , OYEKAN ADEBAYO 
Published: June 2021

Prolyl hydroxylase (PHD) and peroxisome proliferator activated receptor (PPAR)α, known “sensors” of cellular energy and/or oxygen and have been demonstrated to mitigate against oxidative stress, inflammation and fibrosis in cardiorenal pathologies. However, it is not fully known if any commonality exists in their mechanisms of action. This study evaluated the role of Akt/Forkhead box protein FOXO pathway as a possible common target for both PHD and PPARα. In uninephrectomized rats treated with DOCA and 1% NaCl, hypertension was accompanied by cardiac/renal hypertrophy (P<0.05) and marked proteinuria (P<0.01). Accompanying these effects were increases in the expression of TGFβ (72±14%), a marker of fibrosis, p65 (60±7%), an index of inflammation, pAkt (82±10%), a key signaling protein in cellular function, and PHD2 (90±8%), an index of hypoxia but reduced expression of FOXO1 (27±4%) and PPARα (27±6%). Clofibrate, a PPARα ligand, attenuated the hypertension (P<0.05), organ hypertrophy and proteinuria (P<0.05) and blunted the expression of PHD2 (45±6%, P<0.05), pAKt (66±4%, P<0.05), TGFb (P<0.05) and p65 (P<0.05) without changes in MnSOD expression. Combined administration of clofibrate and DMOG, the inhibitor of PHD, exacerbated these effects. These data suggest that FOXO proteins may compliment the activities of PPARα. Moreover, PPARα activation and PHD2 inhibition resulted in similar signaling mechanisms and that combined PPARα activation and PHD2 inhibition may constitute a more effective therapeutic approach in the management of hypertension.Support or Funding InformationNational Institutes of Health grant G12MD007605This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Deletion of Epac1 or Epac2 compromises renal Na+ conservation by decreasing activity of the epithelial Na+ channel (ENaC)
Authors: Tomilin Viktor N , Zaika Oleg , Mei Fang , Cheng Xiaodong , Pochynyuk Oleh 
Published: June 2021

Exchange proteins directly activated by cAMP (Epac1 and Epac2), along with protein kinase A (PKA), are major downstream effectors of the universal intracellular second messenger cAMP, which serves as a nexus of multiple endocrine inputs to regulate renal tubule water and electrolyte transport. We previously demonstrated that deletion of either Epac isoform, namely Epac1 or Epac2, diminishes urinary concentrating ability by reducing fluid reabsorption in the proximal tubule. Here, we employed balance studies in combination with direct electrophysiological assessment of Na+ influx in distal tubule segments from mice with targeted deletion of Epac1 or Epac2 to investigate the role of Epac cascade in tuning urinary Na+ excretion during variations in dietary salt intake. 24 h urinary Na+ levels were comparable in Epac WT and Epac isoform knockouts when animals were subjected to a regular salt intake (0.32% Na+). In contrast, we detected a delayed anti‐natriuretic response during the first 2 days of dietary sodium restriction (<0.01% Na+), which was more pronounced in Epac2 “−/− mice. Consistently, patch clamp analysis in freshly isolated split‐opened collecting ducts found indistinguishable activity (NPo) of the epithelial Na+ channel (ENaC) between Epac WT and Epac2 −/− mice on a regular salt intake: 0.37±0.03 and 0.36±0.05, respectively. Low salt diet greatly increased ENaC activity in Epac WT to 0.75±0.05 as expected, whereas this response was significantly blunted in Epac2 −/− mice (NPo = 0.48 ± 0.06). This was associated with a decrease in both number of active channels per patch and ENaC open probability. In summary, our results support a role of Epac signaling cascade (with a higher contribution of Epac2) in stimulation of ENaC activity by dietary salt restriction. We further propose that reduced ENaC‐mediated Na+ reabsorption at least partially contributes to impaired renal salt conservation in mice with deleted Epac isoforms.Support or Funding InformationNational Institutes of Health (NIH)‐National Institute of Diabetes and Digestive and Kidney Diseases Grants DK119170 (to O.P.), AHA Grant 17GRNT33660488 (to O.P.), ASN Ben J. Lipps Research Fellowship (to V.T.)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Role of body composition and visceral adiposity index in breast cancer
Authors: Peña Elias Cardoso , de Jesús Garduño García Jose , Villanueva Ángel Gómez , Chávez Emilio López , Soto Piña Alexandra E. 
Published: June 2021

Breast cancer and obesity are two diseases that currently occur in a high percentage of women population. Central obesity is an important risk factor for developing breast cancer. Both obesity and cancer are characterized by a chronic state of inflammation in part maintained by cytokines secreted by fat tissue; however, it is not clearly known how they are linked to each other. The aim of this study was to compare body composition and visceral adiposity index (VAI) between women with and without breast cancer. The participants included women 40–60 years old, with stages I and II of breast cancer, who voluntarily accepted to participate in the study. The control group comprised women with BIRADS 1, 2 and 3 mammograms, and the same age span. General sociodemographic data, hereditary family history of breast cancer, gyneco‐obstetric history and histopathological classification of breast cancer were recorded for each participant. Additionally, body composition was evaluated with electrical bioimpedance using an InBody230 equipment. In order to compute the VAI, concentrations of triacylglycerols and high‐density lipoproteins cholesterol (HDL‐c) were measured by colorimetric tests. Data were analyzed using Mann‐Whitney test. The results showed that women with breast cancer presented a higher mean of body mass index (BMI) than the control group (30.4 ± 3.8 Kg/m2 vs 26.5 ± 2.6 Kg/m2, respectively); but these were not significant different (p=.99). The VAI in women with breast cancer was 4.5 ± 0.8, but in the control group was 3.9 ± 0.5; however they were not significantly different. In summary, women with breast cancer showed a higher BMI and VAI, which suggests these markers of obesity might be useful in the diagnostics procedures for this type of cancer, but further analysis in a bigger population is required.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Assessment of the expression profile of circulatory adiponectin and biochemical parameters in broilers
Authors: Lin Yuan‐Yu 
Published: June 2021

Novel studies have found that adipokines can serve as human clinical biomarker or regulate mammalian metabolic functions, but the researches of adipokines on the regulation of metabolic function of avian is still limited. The current study is to investigate the profile of plasma adiponectin and biochemical parameters in broilers, and expect to able to establish basic information and have the deeper possibilities for study metabolic function later.One hundred and fifty Arbor Acres broilers were adapted from the Broiler Management Manual that divided growth into different growth stages. The data of body weight, plasma, and feed consumption were collected at day3, day 7, day 14, day 21, day 28 and day 35. Plasma was used to analyze adiponectin (ADP), macroadiponectin (MADP) and biochemical parameters, such as triglycerides (TG), total cholesterol (TCHO), glucose (GLU), high‐density lipoprotein (HDL) and low‐density lipoprotein (LDL). Results are showed that adiponectin have highly negative correlation with age and macroadiponectin have highly positive relevance with age on both gender in broilers. Moreover, body weight has highly negative correlation (r value, −0.746) with adiponectin and positive correlated with macroadiponectin.This study is first comprehensive explore the profile of adiponectin and its correlation with biochemical values and physiological status in various growth stages which can provide the basis for metabolic study in avian species.Support or Funding InformationFunds for this work were provided by Ministry of Science and Technology, Taiwan (project no. 106‐2313‐B‐029 ‐003 ‐MY2).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 Sepsis on Circulating CTRP3 Levels
Authors: Musick Adam , Shipley Madison M , Tu Fei , Li Chuanfu , Yakubenko Valentin , Peterson Jonathan 
Published: June 2021

Adipose tissue is an active endocrine organ which secrets several pro‐ and anti‐ inflammatory mediators, collectively called adipokines. Our previous work has identified a novel anti‐inflammatory adipokine called C1q TNF Related Protein 3 (CTRP3). Localized overexpression of CTRP3 protects myocardial tissue from lipopolysaccharide (LPS)‐induced sepsis, indicating a potential protective role of CTRP3. However, endogenous regulation of CTRP3 in response to a sepsis event has not been explored. Therefore, the purpose of this project was to explore the potential role of CTRP3 in sepsis by determining the effects of a sepsis event on circulating CTRP3 levels.METHODSGonadal adipose tissue and serum were collected 8 hours after induction of the cecal‐puncture and ligation (CLP) model of sepsis or sham control mice. The circulating levels of CTRP3 were quantified by immunoblot analysis. The transcription levels of CTRP3 in adipose tissue were measured by Real‐Time PCR. In addition, to explore a potential mechanism for a protective role of CTRP3, thioglycollate‐induced peritoneal macrophages were isolated and binding of recombinant CTRP3 protein was determined by imaging flow cytometry.RESULTSCLP‐induced sepsis reduced circulating CTRP3 levels by ~90%, compared to sham treated mice. However, there was no difference in the CTRP3 mRNA level. Further, imaging flow cytometry demonstrated that CTRP3 binds directly to isolated macrophages.CONCLUSIONThe observed reduction in circulating CTRP3 protein levels combined with the absence of changes to the CTRP3 transcription level, indicate that during sepsis CTRP3 is actively removed from the blood. Combine these data support future research to determine if circulating CTRP3 levels are a biomarker indicative of sepsis prognosis. In addition, as CTRP3 binds to and inhibits macrophage activation future research should also determine if restoring circulating CTRP3 levels could reduce the cytokine storm associated with a sepsis event.Support or Funding InformationNIH NIDDK R15DK105496This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.