bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fructose‐induced salt‐sensitive hypertension increases aortic stiffness and induces changes in systemic and renal hemodynamics
Authors: Komnenov Dragana , Gaudette Joshua , Zenner Zachary , Chen Haiping , Rossi Noreen 
Published: June 2021

When high fructose consumption is accompanied by high salt consumption, such as occurs in a typical Western diet, hypertension ensues and the exact mechanism still remains to be identified. Although it has been shown that at least part of the mechanism involves sodium retention by the small intestine and the proximal tubule of the kidney, and reduced renal nitric oxide production, the full spectrum of mechanisms of fructose‐induced salt‐sensitive hypertension and its impact on cardiovascular co‐morbidities remains unknown. The objective of this work was to delineate the longitudinal changes in systemic and renal hemodynamics as a consequence of fructose‐ and salt‐enriched diet. Our central hypothesis is that elevated fructose in the diet predisposes to salt‐sensitive hypertension and initiates changes in both renal and systemic hemodynamics. Previously we found that rats fed 20% fructose for one week develop salt sensitive hypertension within two weeks of high‐salt feeding (4% NaCl). In the present work, using echocardiography we found that fructose‐fed rats displayed increased stroke volume (190.1 ± 9.4 μL vs 145.7 ± 5.8 μL, p < 0.05) and increased left ventricular mass index (1.03 ± 0.06 vs 0.75 ± 0.06), while relative wall thickness remained unchanged. These results are indicative of left ventricular remodeling consistent with eccentric hypertrophy. This is further corroborated by diastolic diameter (6.8 ± 0.2 mm vs 5.9 ± 0.3 mm). Fructose‐fed rats on a high salt (F+HS) diet showed signs of increased aortic stiffness, since the distention to vasodilator phenylephrine was reduced in the ascending aorta (7.1 ± 1.0% from baseline vs 18.2 ± 1.3% from baseline, p<0.05) for the same increase in blood pressure, a result that was not observed in fructose fed rats that were on an normal salt diet (F+NS; 16.1± 2.9%, p < 0.05 vs F+HS). The observed increase in stiffness in the ascending aorta of F+HS rats is likely due to an increase in collagen deposition compared to F+NS and control rats. Finally, we wanted to determine whether the changes in systemic hemodynamics and parameters of cardiac function were paralleled by changes in renal hemodynamics. We measured renal resistive index (RRI) using ultrasound and found that it was elevated in F+HS rats compared to F+NS and control rats. Taken together, these results point to the apparent role of dietary fructose in inducing salt‐sensitive hypertension that is accompanied by increased aortic stiffness and concomitant changes in systemic and renal hemodynamics.Support or Funding InformationVA Merit Award to N.F.R.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effect of Lowering Blood Pressure on Circulating Danger‐Associated Molecular Patterns in Hypertensive Adults
Authors: Stockelman Kelly A. , Bammert Tyler D. , Dow Caitlin A. , Diehl Kyle J. , Garcia Vinicius P. , Greiner Jared J. , Stauffer Brian L. , DeSouza Christopher A. 
Published: June 2021

Elevated blood pressure is associated with increased circulating concentrations of danger‐associated molecular patterns (DAMPs), specifically high‐mobility group box 1 (HMGB1) and heat shock protein 72 (Hsp72). HMGB1 and Hsp72 are prototypical DAMPs that initiate sterile inflammation, drive inflammatory processes and promote atherogenesis. The mechanisms responsible for the increase in circulating HMGB1 and Hsp72 levels in adults with elevated blood pressure is currently unknown. In addition, it is currently unknown whether reducing blood pressure in these individuals results in a concomitant reduction in HMGB1 and Hsp72. Accordingly, the aim of this study was to determine the effects of lowering blood pressure on circulating levels of HMGB1 and Hsp72 in hypertensive adults. To address this aim, we studied 34 middle‐aged adults: 10 normotensive (6M/4F; age: 58±2 yr; BMI: 28.0±1.5 kg/m2; BP: 112/68±2/1 mmHg) and 24 hypertensive (15M/9F; age: 58±1 yr; BMI: 29.5±0.8 kg/m2; BP: 141/88±1/1 mmHg). Within the hypertensive group, 12 received nebivolvol (5 mg/d; 7M/5F; BP: 142/87±2/2 mmHg) and 12 received metoprolol succinate (100 mg/day; 8M/4F BP: 140/89±2/2 mmHg) for 12 weeks. Plasma concentrations of HMGB1 and Hsp72 were determined by enzyme immune‐assay before and after each intervention. Circulating concentrations of both HMGB1 (80.0±3.4 vs 69.5±4.3 ng/mL) and Hsp72 (1.6±0.4 vs 0.8±0.1 ng/mL) were higher (20% and 100%, respectively) in the hypertensive compared with normotensive group. Blood pressure was lowered (P<0.05) to a similar extent (~15 mmHG, systolic) by both nebivolol (125/78±3/2 mmHg) and metoprolol (127/79±3/2 mmHg). However, there was no significant change in circulating HMGB1 or Hsp72 in either the nebivolol (79.9±3.7 vs 81.9±2.5 ng/mL; 1.7±0.7 vs 2.4±1.0 ng/mL) or metoprolol (79.7±6.0 vs 76.0±5.2 ng/mL; 1.5±0.5 vs 1.5±0.5 ng/mL). In summary, although both nebivolol and metorprolol significantly reduced blood pressure, circulating levels of HMGB1 and Hsp‐72 were not significantly affected. These data suggest that: 1) beta‐blockers do not affect circulating DAMPS; and 2) elevations in HMGB1 and Hsp72 in hypertensive adults are not causally‐related to blood pressure.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effects of Essential Oil of Blepharocalyx salicifolius on Cardiovascular Function of Rats
Authors: MOREIRA CLECI MENEZES , Fernandes Maquelen Blanco , Santos Karolina Torres , Schneider Leandro Alves , Da Silva Sue Elle Berro , Sant'Anna Liane Santariano , Paula Fávero Reisdorfer 
Published: June 2021

Some studies reported that herbal interventions with Blepharocalyx salicifolius minimized the high blood pressure in animals. Thus the aim of this study was to evaluate the cardiovascular effects of essential oil from the leaves of the plant. Wistar Kyoto (WKY) and Spontaneously Hypertensive Rats (SHR) with 60 days old were subjected to daily injection of essential oil (10 mg/Kg ip.). At the end of 30 days, the animals were anesthetized, the carotid artery was catheterized to hemodynamic measurements and total blood was collected by puncturing. The cardiovascular measurements performed were systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate, myocardial contractility parameters, angiotensin converting enzyme (ACE) activity and myosin ATPase. The hearts were dissected for left ventricle removal, the papillary muscle was used to assess myocardial contractility and tissue to myosin ATPase and ACE activity determinations. The oil was obtained by hydrodistillation in a Clevenger apparatus and analyzed by GC‐FID and GC‐MS. Molecular modelling studies were performed on components of essential oil of B. salicifolium and Angiotensin I‐Converting Enzyme (ACE‐I) in order to support the understanding of the biological activity. The project was approved by the Ethics Committee for Animal Use from UNIPAMPA under number 05/2016. We identified 34 compounds in the essential oil, the sesquiterpenes representing the largest fraction of the essential oil with 55.9% of constitution, and the main component was the spathulenol with 11.6%. We observed an antihypertensive effect attributed the decrease in SBP and DBP (12% and 23%) in SHR treated with essential oil. The myocardial contractility parameters evaluated by isometric force, sarcoplasmic reticulum activity, inotropic response to the calcium, assessment β‐adrenergic response and strength of tetanic contractions, and serum ACE activity were not modified by the essential oil treatment. However, the myosin ATPase activity was increased 51.6% in SHR and the cardiac ACE activity was decreased 41.5% in SHR and 49% in WKY. Molecular modelling studies were performed on the four main components of essential oil, such as limoneme, viridoflorol, santoline triene and spathulenol. The data suggest the spathulenol, that was the higher concentration component in essential oil, could be the main compound inducing the of ACE‐I activity inhibition. The results obtained in this study reveal the antihypertensive action of B. salicifolius essential oil in SHR and the potential interaction with Renin Angiotensin System without impairment of cardiac function.Support or Funding InformationPPSUS/FAPERGSThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Dual Gain and Loss of Cullin 3 Function Mediates Familial Hyperkalemic Hypertension
Authors: Cornelius Ryan J. , Zhang Chong , Erspamer Kayla J. , Singer Jeffrey D. , Yang Chao‐Ling , Ellison David H. 
Published: June 2021

Familial hyperkalemic hypertension is caused by mutations in with‐no‐lysine (WNK) kinases, or in proteins that mediate their degradation, kelch‐like 3 (KLHL3) and cullin 3 (Cul3). While the mechanisms by which WNK and KLHL3 mutations cause the disease are now clear, the effects of the disease‐causing Cul3Δ403–459 mutation remain controversial. Possible mechanisms including hyperneddylation, altered ubiquitin ligase activity, decreased association with the COP9 signalosome (CSN), and enhanced binding and degradation of KLHL3 have all been postulated. Here, we systematically evaluated the effects of Cul3Δ403–459 using cultured kidney cells. First, using co‐immunoprecipitation, we identified that the catalytically active CSN subunit JAB1 does not associate with the deleted Cul3 4HB domain, but instead with the adjacent α/β1 domain, indicating that resulting secondary structural effects underlie impaired binding. Inhibition of deneddylation, with JAB1 siRNA, increased Cul3 neddylation, but did not mimic the effects of Cul3Δ403–459 with respect to KLHL3 and WNK4, indicating that hyperneddylation is not essential. Next, we prevented Cul3 neddylation by introducing a point mutation at the neddylation site (K712R). The neddylation‐deficient Cul3Δ403–459 K712R construct was still able to significantly degrade KLHL3, indicating that this degradation has both ubiquitin ligase‐dependent and ‐independent components. Pharmacological inhibition of the degradative pathways showed that proteasomal degradation of KLHL3 was enhanced by Cul3Δ403–459; however, autophagic degradation was also upregulated by the Cul3 mutant. Finally, to evaluate whether deficient substrate adaptor was responsible for the disease, we restored KLHL3 to wild type (WT) Cul3 levels. In the absence of WT Cul3, WNK4 was not degraded, demonstrating that Cul3Δ403–459 itself cannot degrade WNK4; conversely, when WT Cul3 was present, as in diseased humans, WNK4 degradation was restored. In conclusion, deletion of exon 9 from Cul3 generates a protein that is itself ubiquitin ligase‐defective, but also capable of enhanced autophagocytic KLHL3 degradation, thereby exerting dominant‐negative effects on the WT allele.Support or Funding InformationNIH R01 DK51496, NIH T32 DK067864, VA 1I01BX002228‐01A1, AHA 16POST3064003, NIH F32 DK112531, National Natural Science Foundation of China 81570634 and 81770706This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effects of hyperglycemia on remodeling of acute myocardial infarction in rats
Authors: Ruiz Gabriela Megumi , de Souza Alcione Lescano , de Souza Leandro Ezequiel , De Angelis Katia , Curi Rui , Irigoyen Maria Cláudia , Malfitano Christiane 
Published: June 2021

Acute myocardial infarction (MI) remodeling consequences for cardiac function were investigated in diabetes (hyperglycemia) induced by streptozotocin (STZ) in rats. The measurements were performed after 15 days of STZ induction (50 mg/kg iv) and/or 48hs of MI. The following parameters were evaluated: levels of FFA, TG (in plasma and the left ventricle–LV) and glycogen in the LV, the cardiac remodeling, the autonomic nervous system activity, and the oxidative stress in the LV. The Wistar rats (n=8 per group) were divided into 4 groups: control (C); control infarcted (CI); diabetic (D); diabetic infarcted (DI). After 15 days of STZ, the MI was induced by left coronary artery occlusion (□ 25% MI area between the CI and DI groups). The CI group had increased: end‐posterior wall thickness (LVPW), interventricular septum thickness the relative wall thickness and reduced LV cavity, as consequence of cardiac remodeling and increased LV mass. The D group had reduced LVPW (0.11 ± 0.001 cm) as compared with the C (0.13 ± 0.003 cm). DI group had increased LVPW (0.14 ± 0.005 cm). The systolic function was not different between groups. However, the D and CI group exhibited increased isovolumetric relaxation time (IVRT ms): D: 34 ± 1; CI: 30 ± 2.4 vs C: 23 ± 0.7 and The E‐wave desaceleration (ms) was increased in D: 50 ± 0.9 vs C: 40 ± 0.6, having diastolic dysfunction in diabetic rats but there was no impairment in MI (DI: 35 ± 2.3). The variance of heart rate (HRV m2) was reduced by diabetes (D: 18 ± 2.5; DI: 25 ± 3) vs the C group (81 ± 3), as well as the low (LF) and high (HF) frequency bands (sympathetic and vagal components). The MI increased in non‐diabetic rats the HRV (CI: 99 ± 14) and the LF (m2) (CI: 1.8 ± 0.5 vs D: 0.6 ± 0.1; DI: 1 ± 0.2). The variance of blood pressure (mmHg) was reduced by diabetes (D: 8.6 ± 0.7; DI: 5.3 ± 0.6) as compared to C (24 ± 3) and CI (18 ± 3) and the LF were increased only in the CI group (2.7 ± 0.17) vs DI group (1 ± 0.2). The MI increased in non‐diabetic rats the lipid peroxidation (1156 ± 125) vs C: 645 ± 111; D: 945 ± 117; DI: 894 ± 112) and both the MI groups increased the anion superoxide, however, only DI had increased antioxidant enzyme activities (catalase, glutathione peroxidase, superoxide dismutase) improving the redox balance after MI. DI group had reduced TG (1.4 ± 0.19) and glycogen (43 ± 7) content in the LV that was increased before the MI (D: 5.4 ± 0.9 vs C: 1.1 ± 0.2; D: 316 ± 79 vs C: 20 ± 5, respectively mg/g of LV). Therefore, the hyperglycemia previous to ischemia promoted a more efficient metabolic response on remodeling and cardiac function with improved oxidative balance.Support or Funding InformationFAPESP, CNPq, and CAPES supported this research.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Fto deficiency reduces infarct size and improves heart function after acute myocardial infarction
Authors: Wehmöller Melanie , Gorressen Simone , Semmler Dominik , Rüther Ulrich 
Published: June 2021

Obesity is one of the major risk factors that can lead to a myocardial infarction and can negatively influence subsequent cardiac remodeling. The onset of obesity is related to different genetic variants of the fat mass and obesity associated gene (Fto). Fto deficient mice were protected from obesity and showed an improved glucose tolerance under a high fat diet. In addition, it is known that Fto acts as an m6A RNA demethylase, whereby it can influence mRNA stability and translation. In a first approach, we used Fto deficient mice to perform an ischemic/reperfusion (I/R) model. At 24 h after reperfusion, Fto deficient mice already had a smaller infarct size compared to their wild type littermates. Over a time period of three weeks, the heart function was investigated by echocardiography. Three weeks after reperfusion, Fto deficient mice showed a preserved heart function and had reduced collagen scar formation compared to wild‐type control mice. Initial molecular studies indicated a reduction of the mTORC1 pathway and consequently a down regulation of S6K phosphorylation. For a first approach of therapeutic intervention, we used the Fto inhibitor rhein, which binds the active center of Fto and thereby inhibits its demethylase activity. Wild type mice were pre‐treated with rhein or the solvent over three weeks before the I/R procedure was performed. The rhein‐treated mice showed a significant reduction in the infarct size compared to the solvent treated littermates. In this study, we demonstrated that Fto deficiency can modulate the outcome of a myocardial infarction by improving left ventricular function and reduction of the infarct size.Support or Funding InformationSupported by the Deutsche Forschung Gesellschaft (DFG) as Part of the SFB 1116 (project number 236177352)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
TREATMENT WITH HYPERBARIC OXYGENATION AFTER 6 HOURS OF AN ACUTE MYOCARDIAL INFARCTION IN RATS
Authors: Juan‐Dominguez Vania Don , Rios‐Garcia Eduardo Castillo , Gutierrez‐Martinez Luis Alberto , Guevara‐Balcazar Gustavo , Castillo‐Hernandez Maria Carmen 
Published: June 2021

Acute myocardial infarction has been placed in the leading cause of death in the world. Coronary interventionism is the gold standard in the treatment of AMI, however its therapeutic window is very limited. The decrease in the area of myocardial infarction and hemodynamic improvement have been reported with the use of HBO therapy in the ongoing AMI, as well as angiogenesis, decreased inflammation and useful as ischemic preconditioning.MethodologyAn experimental study was designed to determine the effect of HBO on the rat cardiomyocyte after 6 hours of an AMI induced by ligation of the anterior descending coronary. The HBO was administered through a 100% hyperbaric chamber, at 2 ATA, for one hour daily. The size of the infarcted area was macroscopically measured, and antioxidant enzymes were evaluated. Six groups were compared.ResultsA statistically significant decrease of the infarcted area was obtained from the 3rd session of HBO. Regarding oxidative stress, significant results were obtained for TBARS, TAS and 3‐NT from the 5th session with HBO.ConclusionHyperbaric oxygen therapy shows a beneficial effect after 3 days of the induction of AMI, this is reflected by a decrease in the infarcted area; and after the 5th day reflected by a decrease in TBARS and 3‐NT.Support or Funding InformationSIp, COFAA, IPNThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
AT1 Receptor Blockade Improves Mitochondrial Activity in Insulin Resistant but not Type II Diabetic Hearts
Authors: Thorwald Max Andrew , Rodriguez Ruben , Nakano Daisuke , Nishiyama Akira , Ortiz Rudy 
Published: June 2021

Hyperglycemia increases the risk of oxidant overproduction in the heart through activation of a multitude of pathways. Oxidation of mitochondrial enzymes may impair their function resulting in accumulation of intermediates and reverse electron transfer, contributing to mitochondrial dysfunction. Furthermore, the renin‐angiotensin system (RAS) becomes inappropriately activated during metabolic syndrome, increasing oxidant production through NAPDH assemblage. To test the acute effects of an oral glucose tolerance test (oGTT) on the insulin resistant and type II diabetic hearts, 16 and 25 week old animals were given a glucose tolerance test prior to dissection. Adult male rats were randomly assigned to three groups prior to dissection (n= 5–8 animals/group/time point): 1) Long Evans Tokushima Otsuka (LETO; lean strain‐control), 2) insulin resistant, obese Otsuka Long Evans Tokushima Fatty (OLETF), and 3) OLETF + angiotensin receptor blocker (ARB; 10 mg olmesartan/kg/d x 6–8 weeks). Hearts were collected at T0, T60, and T120 minutes post‐glucose infusion and at T0, T180, and T360 in 25‐week‐old animals. Aconitase activity was not changed between LETO and OLETF rats at T0, but was increased five‐fold with ARB treatment. At T60 aconitase activity was decreased 69% in OLETF from LETO, but ARB treatment increased activity six‐fold. AT 25 weeks of age aconitase activity was two‐fold higher in OLETF compared to LETO and remained unchanged through T360. ARB treatment lowered this activity to LETO levels at T0 only. Complex I activity had no detectable difference between LETO and OLETF in 16 week old animals; however, ARB increased activity by 50%. However, in 25 week old animals complex I was lowered 32% from LETO and ARB treatment had no effect on complex I activity. At T60, complex II activity was decreased 30% from LETO in OLETF rats, and ARB treatment increased complex II activity by 79%. In 25 week old animals OLETF rats had increased complex II activity at T180 by 34%, which then was restored to baseline by T360. ARB treatment increased activity by 26%, but maintained this increase over the 6 hour span. These data demonstrate the protective effects of AT1 blockade on cardiac mitochondrial function during the manifestation of insulin resistance, but demonstrate that its protective effects diminish as animals transition into a frank diabetic stage.Support or Funding InformationM. Thorwald and R. Rodriguez were supported by NIH NCMHD9T37MD001480. R.M. Ortiz was partially supported by NIH NHLBIK02HL103787. Research was partially funded by NIH NHLBIR01HL091767.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Insulin Signaling Displayed a Differential Tissue Specific Response to Low Dose Dihydrotestosterone in Female Mice
Authors: Andrisse Stanley , Wu Sheng 
Published: June 2021

Hyperandrogenemia and hyperinsulinemia are believed to play prominent roles in polycystic ovarian syndrome (PCOS). We explored the effects of low dose dihydrotestosterone (DHT) on insulin signaling in metabolic and reproductive tissues in a female mouse model. Insulin resistance in the energy storage tissues is associated with type 2 diabetes. Insulin signaling in the ovaries and pituitary either directly or indirectly stimulates androgen production. Energy storage and reproductive tissues were isolated and molecular assays were performed. Livers and WAT from DHT mice displayed lower mRNA and protein expression of insulin signaling intermediates. However, ovaries and pituitaries of DHT mice exhibited higher expression levels of insulin signaling genes/proteins. Insulin‐stimulated p‐AKT levels were blunted in the livers and WAT of the DHT mice but increased or remained the same in the ovaries and pituitaries compared to controls. Glucose uptake decreased in liver and WAT but was unchanged in pituitary and ovary of DHT mice. Plasma membrane GLUTs were decreased in liver and WAT but increased in ovary and pituitary of DHT mice. Skeletal muscle insulin signaling genes were not lowered in DHT mice compared to control. DHT mice did not display skeletal muscle insulin resistance. Insulin‐stimulated glucose transport increased in skeletal muscles of DHT mice compared to controls. DHT mice were hyperinsulinemic (HI). However, the differential mRNA and protein expression pattern was independent of hyperinsulinemia in cultured hepatocytes and pituitary cells. These findings demonstrate a differential effect of DHT on the insulin‐signaling pathway in energy storage versus reproductive tissues independent of hyperinsulinemia.Support or Funding InformationThis work was supported by the National Institutes of Health (Grants R00‐HD068130 04 to S.W. and 5T32DK007751‐18 to S.A.). Technical support was provided by the Integrated Physiology Core of the Baltimore DRTC (P30DK079637). Disclosure Summary: The authors have nothing to disclose.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.