bluuebunny/crossref_metadata_2025_split huggingface dataset:
His and Her Computational Models of Long‐term Blood Pressure Regulation
Authors: Leete Jessica , Layton Anita 
Published: June 2021

Hypertension is a global health challenge. Hypertensive men and women are typically treated with the same approach, with less effective outcome in women. To address the critical need to better understand the mechanism of blood pressure control in both men and women, we have developed sex‐specific computational models of long‐term blood pressure control. The model represents sex differences in the kidney's pressure natriuresis response, whereby increases in renal perfusion pressure lead to increases in Na+ excretion; that in turns lowers salt and water retention and reduces effective circulating volume. Females tend to exhibit a leftward shift in the pressure‐natriuresis relation relative to males. The model also includes detailed representation of the renin‐angiotensin aldosterone system (RAAS), a non‐sex hormonal system critical for maintaining blood pressure and effective circulating volume. Major sex differences in the RAAS have been identified, including how substrate is produced and how angiotensin interacts with receptors. Those sex differences are included in the model. Using the developed model, we test the hypothesis that RAAS‐mediated anti‐natriuretic (and thus blood pressure increasing) effects are more severe in males than females, leading to more hypertension‐induced injury in males.Support or Funding InformationThis research was supported in part by the National Institutes of Health: National Institute of Diabetes and Digestive and Kidney Diseases, grant R01DK106102.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Plantago asiatica seed Extracts Alleviated Blood Pressure of Phase I –Spontaneous Hypertension Rats
Authors: Chou Chi‐Chen , Lue Sheng‐I , Fu Yaw‐Syan , Weng Ching‐Feng 
Published: June 2021

Introduction and hypothesisThe seed of Plantago asiatica is a traditional Chinese medicine with diuretic and anti‐inflammatory effects. Of note hypertension is a multifactorial cardiovascular disorder involved in variety genetic and environmental factors and it is a major risk factor for heart disease, heart attack or stroke. Phase‐1 hypertension (P1‐HT) is considered to be critical phase in the beginning stage of high blood pressure. In this study, P. asiatica seed extract (PSE) was administrated in spontaneous P1‐HT rats to evaluate the efficacy of antihypertension.MethodsIn this study, arterial pressures of each P1‐HT rats were recorded for 5 minutes by intravascular femoral artery catheter served as a reference value for prior to treatment. In acute antihypertensive effect test, P1‐HT rat gavage received 0.36 g/kg Bwt of PSE or equal volume of water by dissolved in distilled water and the arterial pressures were recorded continuously for 1 hr. In chronic antihypertensive effect test, P1‐HT rats gavage received 0.36 g/kg Bwt day of PSE or equal volume of water for 4 weeks. Students–t test and one way ANOVA were used for statistical analysis. Statistical significances were set at a P< 0.05.ResultsFirstly, the monitor of rat blood pressure was confirmed that the systolic, diastolic and mean arterial pressures of this spontaneous P1‐HT rat are stably keeping in 150±20 mmHg, 92±30 mmHg, and 115±15 mmHg, respectively. The acute antihypertensive effects of this new breeding spontaneous P1‐HT rat could appear within 15 min. after PSE oral administration and lasting more than 1 hr. This acute antihypertensive effect of PSE could decrease the systolic pressure of P1‐HT rat for 28 mmHg, and diastolic pressure for 16 mmHg when simultaneously compared with verapamil as a reference drug, but there were no significant difference in the pretreated reference value of both acute PSE and the control treated groups of P1‐HT rat. The reducing tendency of blood pressure was also found in 4 weeks PSE treatment as compared with the untreated control.ConclusionsThis new breeding P1‐HT modeling rat has a stable phase‐1 hypertensive phenotype after sexually mature and it is suitable for use in hypertensive studies. The oral administration with PSE can effectively reduce blood pressure within a quarter and last more than 1 hr while taking PSE daily can control the severity of hypertension.Support or Funding InformationMOST‐104‐2320‐B‐259‐001‐MY3This 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 Glucagon‐Like Peptide‐1 Receptor Agonist (GLP1RA) on Hypertension‐Induced Atrial Remodelling
Authors: Zhang Zhe Yu 
Published: June 2021

IntroductionAtrial fibrillation (AF) is one of the most important cause of stroke. Hypertension (HT)‐induced atrial remodelling is the most common risk factor for AF. Studies have shown that patients receiving GLP‐1 receptor agonist have reduced AF. This study investigates the effect of GLP1RA on AF prevention.MethodHT was induced in 15 swines using angiotensin II infusion. At 8 weeks (8W) GLP1RA was randomly given to the swines for 8W in 1:2 ratio. Effect of GLP1RA of atrial remodelling was assessed at 0W, 8W and 18W.ResultsAt 0W and 8W, there were no differences in body weight, blood pressure, interventricular septal thickness at diastole (IVSDD), left ventricular end‐diastolic pressure (LVEDP), −dP/dt or end‐diastolic pressure volume relationship (EDPVR) between the treatment (n=5) and control (n=10) group. At 18W, there were no significant differences in body weight (78.2±2.26kg vs 80.4±2.67kg, P=0.558), SBP (144±5.1 mmHg vs 169.2±7.3 mmHg, P=0.229) or DBP (94±5.1 mmHg vs 105.3±5.6 mmHg, P=0.520) between the two groups. Nevertheless, IVSDD (0.96±0.09 mm vs 1.19±0.03 mm, P<0.05), LVEDP (8±0.86 mmHg vs 10±1.14 mmHg, P<0.05), −dP/dt (−943.6±94.7 vs −1387.5±58.4, P<0.05) and EDPVR (0.224±0.04 vs 0.434±0.03, P<0.05) were significantly lower in the treatment group. Biomarker study also showed a reduced TGF‐b1 (178.9±7.6pg/mL vs 348.5±24.1pg/mL, P<0.05) and sICAM‐1(0.823±0.56 ng/mL vs 2.308±0.378 ng/mL, P<0.05) in the treatment group. Serum TNF‐a (36.92±0.81 pg/mL vs 56.03±2.66 pg/mL, P<0.05), ROS (13.86±3.8 uM vs 30.27±13.9 uM, P<0.05) and MMP‐2 (19.08±0.39 ng/mL vs 28.16±0.42 ng/mL, P<0.05) expression were all significantly lower in the treatment compared with control group.ConclusionGLP1RA halted the progression of HT‐induced LV functional and structural remodeling independent of body weight or blood pressure but associated with reduced profibrotic markers, inflammatory markers and oxidative stress.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Nephron‐wide deletion of NOS3 impairs salt excretion and causes hypertension during high salt intake via altered NKCC2 activity
Authors: Gao Yang , Stuart Deborah , Takahishi Takamune , Kohan Donald E. 
Published: June 2021

In vitro studies suggest that nephron nitric oxide synthase (NOS3) regulates urinary Na+ excretion (UNaV) and blood pressure (BP). To assess whether NOS3 is indeed involved in the physiological regulation of UNaV and BP, mice with doxycycline‐inducible nephron‐wide deletion of NOS3 were generated. These mice were homozygous for loxP‐flanked exons 9–12 of the NOS3 gene (contains the calmodulin binding site) and hemizygous for Pax8‐rtTA and LC‐1 transgenes (Pax8 promoter‐rtTA confers nephron‐specific targeting and LC‐1 transgene contains doxycycline/rtTA‐inducible Cre recombinase). Mice were treated with either vehicle (controls) or doxycycline (knockouts, KO) at 1 month of age for 12 days and studied at ~3 months of age. Nephron‐specific NOS3 KO mice had renal‐specific NOS3 gene recombination, reduced NOS3 mRNA levels in microdissected nephron segments, and decreased urine NOx excretion. In response to chronic high salt load, KO mice had increased mean arterial pressure (103 ± 2 mmHg in controls and 118 ± 3 mmHg in KO, N=6, p<0.05), reduced renal NOS3 protein expression (43 ± 8.4% of controls, N=5–6, p<0.05), and enhanced cumulative Na+ retention. In response to acute salt load (1.5 ml saline i.p. injection), KO mice had delayed urinary Na+ excretion vs. controls; this delayed UNaV was abolished by furosemide, but not hydrochlorothiazide or amiloride. After 4h of an acute salt load, KO mice had decreased NOS3 protein expression (19 ± 6.5% of controls, N=5–6, p<0.05) and an increased ratio of phosphorylated/total NKCC2 (162 ± 14.1% of controls, N=5–6, p<0.05). No differences in NHE3, NCC (phosphorylated/total), or ENaC isoforms were noted 4 h after an acute salt load or after chronic salt loading. No sex‐dependent differences in UNaV or BP were observed. In summary, these findings support the notion that nephron NOS3 is involved in acute and chronic control of renal Na+ excretion and BP during high salt intake. Thick ascending limb NKCC2 may be the major transporter involved in nephron NOS3 regulation of renal Na+ excretion and BP.Support or Funding InformationThis research was supported by NIH P01 HL095499This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Reduced Arrhythmogenic Potential of Ventricular Paired Pacing During Myocardial Infarction
Authors: Stein Paul M. 
Published: June 2021

Since the 1960's, the clinical use of ventricular paired pacing (VPP), a form of continuous postextrasystolic potentiation, to augment cardiac function in cardiogenic shock has been prevented by the stigma of ventricular arrhythmogenesis. Historically, this perception was based on very limited human data on the sickest of the sick when many current medical treatments were long into the future. One such treatment is the use of β‐adrenergic receptor blockade, well accepted now, but antithetical then. A meta‐analysis of canine studies of myocardial infarction was performed to understand the effect β‐blockade had on the incidence of ventricular fibrillation during the VPP treatment (References: Singer, D. H. et al. Bull. N. Y. Acad. Med. 41: 652–669, 1965; Rothfeld, E. L. et al. Am. J. Cardiol. 23: 224–228, 1969; Karayannacos, P. E. et al. Ann. Thorac. Surg. 27:34–41, 1979). Infarctions in 48 animals were produced through ligation of the entire or one to three branches of the left anterior descending coronary artery or the entire left circumflex coronary artery with (n=24) or without i.v. pronetholol or propranolol (n=24). Following ligation, in all studies, VPP had a marked inotropic effect. Without β‐blockade, 16 went into ventricular fibrillation during VPP, while only 5 with β‐blockade did.Statistics

Comparison of Proportions Difference=45.83%, 95% Confidence Interval=15.21–68.22, χ2 = 10.03, P<0.002, Contingency Coefficient=0.42;
Odds Ratio=7.60, 95% Confidence Interval=2.07–27.90, z Statistic=3.06, P<0.005;
Relative Risk=3.20, 95% Confidence Interval=1.40–7.34, z Statistic=2.75, P<0.01;
Number Needed to Treat=2.18, 95% Confidence Interval=4.78–1.41.
In conclusion, while not eliminating the potential for induced ventricular fibrillation, the anti‐arrhythmic effect of β‐adrenergic receptor blockage did significantly reduce the incidence from 67% to 21%, a 69% decrease. A clinical trial is necessary to confirm these findings under today's medical landscape, when many heart attack victims are already taking β‐blocking drugs and standard cardiogenic shock therapy includes the powerful anti‐arrhythmic drug amiodarone. Until then, ventricular paired pacing should not be categorized as overtly arrhythmogenic in cardiogenic shock. It does, however, contain a minor potential that must be carefully watched for with ubiquitous defibrillators.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Day 1 Post‐Myocardial Infarction Cardiac Macrophage Transcriptomic Signatures that Link to LV Infarct Wall Thinning
Authors: Mouton Alan Joseph , Ma Yonggang , DeLeon‐Pennell Kristine , Garrett Michael , Lindsey Merry 
Published: June 2021

We evaluated the relationships between the macrophage transcriptome at day 1 following myocardial infarction (MI) and infarct wall thinning. C57BL/6J male mice (3–6 months old) were subjected to permanent coronary artery ligation to induce MI, and macrophages were isolated from the infarct region at day 1 post‐MI. Day 0 no MI cardiac macrophages served as the negative control. Whole transcriptome analysis was performed using next‐generation RNA sequencing (Illumina NextSeq 500 platform) on n=4 pooled sets for each time, representing a total of 59 mice. Infarct wall thinning (Day 0 – Day 1) was assessed by echocardiography. A total of 16,696 genes were quantified and passed quality control (FPKM > 0 for at least 3 replicates per group). Of these, 3,062 were differentially expressed (fold change ≥ 2.0, p<0.05), of which 1,019 were upregulated and 2,043 were downregulated. Gene ontology pathways enriched for the upregulated genes included inflammatory response and response to hypoxia, while pathways enriched for the downregulated genes included extracellular matrix organization. To determine potential contributions of individual genes to the wall thinning phenotype, large scale correlation analysis was performed. Of the 3,062 differentially expressed genes, 119 positively correlated with the decrease in wall thickness, while 93 negatively correlated. Of interest, positive correlations between several pro‐inflammatory genes and wall thinning were observed, includingTlr1 (r=0.99, p=0.01), Tnfrsf1b (r=0.95; p=0.047), Hrh4 (r=0.96; p=0.036), and Stat5a (r=0.95; p=0.048), all of which play pro‐inflammatory roles in response to inflammatory stimuli. Genes that negatively correlated with wall thinning included Vegfa (r=−0.96, p=0.04) and Nfkbie (r=−0.99, p=0.009), which are negative regulators of inflammation. Of the positively correlated genes, NF‐kappaB was a major enriched pathway (p=0.009), suggesting excessive NF‐kappaB signaling in macrophages exacerbates post‐MI wall thinning. For negatively correlated genes, Kit signaling, which has been linked to immune suppression and the anti‐inflammatory M2 phenotype, was a major enriched pathway (p=0.00001). Combined, these results indicate that promoting pro‐inflammatory and limiting anti‐inflammatory gene expression in post‐MI day 1 cardiac macrophages is directly linked to LV wall thinning.Support or Funding InformationFunding: NIH GM103328, GM103476, GM104357, GM114833, GM115428, HL051971, HL075360, HL105324, HL129823, AHA 15SDG22930009, and VA 5I01BX000505 and IK2BX003922This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Previously Exercise Training in Ovariectomized Rats Prevents Inflammatory Status of Myocardial Infarction by Vagal Tonus Increase
Authors: Ruberti Olivia Moraes , de Paula Eunice Mendonça , Souza Andressa Silva , Viana Laís Rosa , Delbin Maria Andreia , Rodrigues Bruno 
Published: June 2021

The aim of this study was to investigate the preventive effects of aerobic training (AT) in ovariectomized rats submitted to myocardial infarction (MI). Female Wistar rats were ovariectomized and divided into four randomized groups: sedentary sham (SS), sedentary + MI (SI), AT + sham (TS), AT + myocardial infarction (TI). Exercise training was performed on a treadmill (60 to 75% of the maximum running speed) in ovariectomized rats before the MI. After 8 weeks of AT, the MI area was lower in the TI group compared to SI. The sympathetic tonus was reduced in TS (68±3 bpm) and TI (77±3 bpm) groups as compared to SI (98±4 bpm), but higher in TI compared to TS. The vagal tonus was substantially increased in TI (40±4 bpm) in comparison to SI (23±3 bpm). The AT reduced inflammatory cytokines profile on left ventricle, as interleukin‐6 (IL‐6: 68.2±7.2 vs. 148.9±6.1 pg/mg prot), IL‐1β (86.7±10.2 vs. 135.9±12.2 pg/mg prot), interferon‐γ (19.3±3.3 vs. 38.7±4.3 pg/mg prot) and tumor necrosis factor‐α (TNF‐α: 19.6±3.8 vs. 42.3±5.8 pg/mg prot), as well as increased IL‐10/TNF‐α ratio in TI rats as compared to SI. Vagal tonus was negatively correlated with TNF‐α (r=−0.75; P<0.001) and positively associated to interleukin‐10 (r=0.77; P<0.001). These findings indicate that AT displayed ventricular protective effects on the ovariectomized rats submitted to MI. Additionally, protective effects regarding left ventricle inflammatory status may have occurred in the light of cholinergic anti‐inflammatory pathway.Support or Funding InformationCAPES, FAPESP and CNPqThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Myocardial ischemia/reperfusion in rats: characterization of cardiac injuries
Authors: Omoto Ana Carolina Mieko , Gava Fábio Nelson , Fazan Frederico Sassoli , Silva Carlos Alberto Aguiar , Silva Hadder Batista , Nappi Camilla Rizzo , Parente Juliana Montenegro , da Costa Rafael Menezes , Salgado Helio Cesar , Fazan Rubens 
Published: June 2021

Coronary reperfusion is an important tool to limit infarct size and preserve cardiac function after acute myocardial infarction. However, the reperfusion of acutely ischemic myocardium can induce arrhythmias and cardiomyocyte death, a phenomenon known as myocardial reperfusion injury. The study of the mechanisms and the search for therapies to protect the heart from reperfusion injury is an important field of research. The aim of this study was to evaluate mophofunctional and molecular aspects involved in a rat model of acute myocardial ischemia followed by reperfusion (IR). Male Wistar rats (N=47) were anesthetized with ketamine and xylazine (50 and 10 mg/kg, ip) and subjected to myocardial IR by temporary (30 min) ligation of left descending coronary artery. Control rats (N=7) underwent the same surgery without coronary ligation. After 4 weeks 45% of the rats subjected to IR showed no cardiac lesion (NL) while 38% presented mild (ML) and 17% large (LL) lesion of the heart. Cardiac function, evaluated by echocardiography, was impaired in all rats subjected to IR, independently of the degree of cardiac lesion. Interstitial fibrosis, quantified in non‐infarcted myocardium, was 11±0.8% in control rats and was found increased in rats with IR (19.7±1.4, 19.4±1.2 and 21.6±1.2% in rats with NL, ML and LL, respectively). Activity of matrix‐metalloproteinase‐2 was higher in the myocardium of rats subjected to IR (0,44 to 0.48 AU) as compared to their control counterparts (0.22 AU). Moreover, concentration of superoxide anion in the myocardium of rats subjected to IR was higher (176±44, 127±13 and 108±30 RLU/mg of protein in rats with NL, ML and LL, respectively) as compared to their controls (50±5 RLU/mg of protein). Finally, hydrogen peroxide was measured 86±29 nmol/mg of protein in myocardium of control rats and was found markedly higher (1077±192, 1194±238 and 639±117 nmol/mg of protein in IR rats with NL, ML and LL, respectively) in the animals subjected to IR. These results show that IR leads to distinct degrees of myocardial injury in a rat model, which contributes to cardiac dysfunction over time. Reactive oxygen species (O2− and H2O2) and MMP‐2 seems to be involved in cardiac dysfunction and heart failure development after reperfusion.Support or Funding InformationFinancial support: CNPq (870308/1997‐1) e FAPESP (2013/20549‐7).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
CD8 T‐cells have a biphasic role during post‐myocardial infarction cardiac remodeling
Authors: DeLeon‐Pennell Kristine Y. , Lindsey Merry L. , Flynn Elizabeth , Menick Donald R. 
Published: June 2021

Historically, the role of adaptive immunity has not been considered to play a major role in the wound healing response to myocardial infarction (MI), due to the low number of these cells within the infarct region. While recent studies have linked elevated CD8+ T‐cell counts (>1065 cells/mm3) with a 2‐fold decrease in post‐MI survival in humans, the exact mechanisms by which CD8+ T‐cells impair cardiac wound healing post‐MI are not thoroughly understood. We hypothesized that CD8+ T‐cells regulate the inflammatory response leading to decreased survival and cardiac function post‐MI. We performed permanent occlusion of the left anterior descending coronary artery on C57BL/6J wild‐type mice (WT; 4.5±0.1 months of age; n=6 males and females) and CD8atm1Mak mice (Null; 4.1±0.2 months of age; n=6 males and females) that are deficient in functional cytotoxic T‐cells. Null had improved day 7 survival (75%) compared to WT (43%; p<0.0001). Interestingly, 100% of Null who died did so due to cardiac rupture of the left ventricle (rupture/total deaths; 2/2) whereas only 38% of WT (3/8; p<0.0001) died of cardiac rupture. In addition, Null died during the early post‐MI phase (at days 1–2). Post‐MI mortality in WT does not usually occur until after day 3, suggesting CD8+ T‐cells may be protective during the early post‐MI phase by limiting immediate remodeling. Echocardiography measured at day 7 post‐MI showed improved cardiac physiology, as indicated by fractional shortening in Null (11±3%) compared to WT (4±1%; p<0.05) implicating CD8+ T‐cells as a negative regulator of wound healing during the later phase post‐MI. In conclusion, our data suggests CD8+ T‐cells play a biphasic role during post‐MI cardiac remodeling by being protective early and detrimental later.Support or Funding InformationThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.