bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P148: Safety And Efficacy Of Edaravone Dexborneol Versus Edaravone Alone For The Treatment Of Acute Ischemic Stroke Patients With Hypertention: Analysis From Taste Trial
Authors: Xu Jie , Wang Yongjun
Published: August 2021

Background and Aims:
Evidenced by TASTE phase III trial, 90-day good functional outcomes favored the edaravone dexborneol group versus edaravone group when administered within 48 hours after Acute Ischemic Stroke (AIS). The present study aimed to investigate the effects of edaravone dexborneol versus edaravone in AIS patients with hypertension medical history.

Methods:
This study was a subgroup analysis of the TASTE trial with hypertension medical history. The primary outcome was the proportion of patients with modified Rankin Scale (mRS) score ≤1 on day 90 after randomization. The secondary outcome was the mRS score on day 90. The safety endpoints were the incidences of adverse events, serious adverse events and deaths. Analyses were by intention to treat.

Results:
We included 767 AIS patients with hypertension (390 in edaravone dexborneol group, 377 in edaravone group) in this analysis. Among them, 252 (64.62%) in edaravone dexborneol group versus 199 (52.79%) in edaravone group reached mRS score ≤1 on D90, revealing significantly higher proportion of mRS score ≤1 on D90 in edaravone dexborneol group (OR 1.63 [95% CI, 1.22-2.18]; P<0.001). Significant differences occurred between two groups in mRS score on D90 ([OR 1.32 [95% CI, 1.02-1.72]; P=0.038). The safety outcomes indicated that the two groups were similar in incidences of adverse events (366 [93.85%] versus 352 [93.37%], p=0.787), serious adverse events (48 [12.31%] versus 34 [9.02%], p=0.1405) and number of deaths (6 [1.54%] versus 4 [1.06%], p=0.56).

Conclusion:
This analysis demonstrated that AIS patients with hypertension receiving edaravone dexborneol had better functional outcomes than those with edaravone, which provided evidences for the clinical application of edaravone dexborneol in AIS patients with hypertension.

Keywords:
Edaravone dexborneol, Acute ischemic stroke, Hypertension, mRS score
Abstract P157: Altered ERK-mediated Control Of AgRP And Metabolic Rate During Obesity
Authors: Ritter McKenzie L , Balapattabi Kirthikaa , MORSELLI LISA , Sigmund Curt D , Grobe Justin L
Published: August 2021

Adaptation of resting metabolic rate (RMR) contributes to the maintenance of human obesity, yet the control of RMR - and how this system changes during obesity - remains poorly defined. Leptin normally suppresses Agouti-related peptide (AgRP) expression in the arcuate nucleus of the hypothalamus (ARC) to disinhibit melanocortin-mediated stimulation of RMR. Leptin stimulates ERK signaling in the ARC (a known suppressor of AgRP), and the inhibition of ARC ERK attenuates thermogenic sympathetic nervous activity responses to leptin. Diet-induced obesity (DIO) increases leptin, but paradoxically exaggerates ARC AgRP expression and causes RMR adaptation. Thus, we hypothesize that leptin increases ERK signaling in AgRP cells, to reduce AgRP and thereby ultimately increase RMR, but that this signaling mechanism becomes dysfunctional during DIO. Leptin application to GT1-7 cells (a model of AgRP neurons) increased pERK/ERK ratio (1 uM, 15 min leptin n=3, 2.9-fold of vehicle n=2, p<0.05). In chow-fed adult mice, leptin injection caused an increase in ARC pERK/ERK ratio (2 ug/g ip 30 min leptin n=11, +43.8% vs saline n=9, p<0.05) without affecting total ERK levels (normalized to beta-actin). DIO caused increases in endogenous plasma leptin and an increase in ARC pERK/ERK ratio (HFD n=5, +54.4% vs chow n=4, p<0.05) without affecting total ERK levels - yet, canonical transcriptomic effects of ERK (ie, suppression of AgRP) were lost. Finally, reanalysis of our published single-nucleus RNAsequencing dataset describing the transcriptome of ARC after DIO demonstrates loss of canonical effects of increased ERK signaling specifically within the AgRP cell type. Together, these findings indicate that although DIO is associated with expected increases in ERK activation in AgRP neurons and the ARC, the consequences of ERK signaling are attenuated. We therefore hypothesize that DIO results in RMR adaptation through changes in signaling mechanisms that link ERK to its downstream targets, such as AgRP. Ongoing studies are focused on the development of novel animal models with tamoxifen-dependent conditional deletion of ERK within the adult AgRP neuron, to test whether loss of ERK signaling is sufficient to explain changes in ERK/AgRP/RMR control during DIO.
Abstract P161: Blood Pressure And Vascular Stiffness With Increased Body Weight In Young People In The Aspect Of The Obesity Paradox
Authors: Evsevyeva Maria , Eremin Michail , Rostovtseva Maria , Galkova Ilona , Kudrjavtseva Victoria , Gachkova Irina
Published: August 2021

Background:
The relationship of arterial stiffness, which is marker of vascular age, with the main risk factors (RF) was studied mainly in adults and elderly. Purpose - to evaluate associations of various body mass (BM) with vascular stiffness, blood pressure (BP) and some other RF in young people.

Material and Methods:
Within the framework of the National Preventive Project "University Territory of Health", 264 students (93 boys and 171 girls) aged 18-25 years were evaluated for BP and profile of metabolic RF - total cholesterol (TC), low-density lipoproteins (LDL), triglycerides (TG), high-density lipoproteins (HDL) and glucose. Vascular stiffness was determined using cardio-ankle vascular index (CAVI), which was measured using diagnostic complex VaSera-1500 (Fucuda Denshi, Japan). Students were divided into groups according to BM-index: 1group - insufficient BM; 2 group - normal BM and 3 group - overweight. Data processing was performed using software package "Statistica 10.0" (StatSoft Inc, USA).

Results:
It turned out CAVI values in three observation groups, formed by BM indicator, in boys averaged 6.8 ±0.2, 5.9 ± 0.1 and 5.4 ± 0.1, and in girls - 6,1 ± 0,11, 5,9 ± 0,05 and 5,7 ±0,13. In boys, differences between groups on this indicator reached significant level (p = 0,032). At same time, systolic and diastolic BP from first to third group rose in boys by 9 and 2, and in girls - by 11 and 4 mm Hg. TC, LDL and TG also increased from first to third group in boys by 0.5, 0.4 and 0.5, and in girls - by 0.6, 0.7 and 0.65 mmol/l. HDL decreased in these groups in boys by 0.07, and in girls - by 0.37 mmol/l. The glucose level from first to third group increased by 0.12 in boys and 0.14 mmol/l in girls.

Conclusion:
A decrease in the vascular stiffness index CAVI was found among young people as their BM increased. It is noteworthy that in young people with an increased BM, positive changes in vascular rigidity occur in the presence of negative changes in hemodynamic and metabolic parameters, which are more significantly represented among girls. Further in-depth research is needed to clarify the mechanisms that regulate the relationship between metabolic status of young people and peculiarities of their vascular remodeling.
Abstract P163: Prevention Of Cardiac Fibrosis By Dietary Sodium Restriction During Metabolic Syndrome: Involvement Of Endothelial To Mesenchymal Transition
Authors: MIMOUNI Mohammed , DARLET Solene , JOVER Bernard F , JEANSON Laura , BLANCHARD Marie-Pierre , LAJOIX Anne-Dominique , DESMETZ Caroline
Published: August 2021

In a rat model of metabolic syndrome (MS), our previous studies have shown that dietary sodium restriction prevents both metabolic and cardiac damages associated with MS. Our aim is now to investigate whether the beneficial effects of sodium restriction could be mediated by endothelial to mesenchymal (EndoMT) transition in the myocardium thereby preventing cardiac fibrosis.High fructose (60%) Sprague Dawley rats were divided into 2 groups: low sodium (<0.01% NaCl, N=20) or normal sodium (0.65% NaCl, N=20) diet for 8 weeks. EndoMT was investigated by q-PCR, WB, and IF on the left ventricles. Transcriptomic analysis was performed using Agilent Rat Gene Expression Microarray. After 8 weeks, fructose-fed rats on normal sodium diet were insulin-resistant and hypertensive, both abnormalities being significantly prevented by sodium restriction. In left ventricles, two mesenchymal proteins, α-smooth muscle actin (αSMA) and vimentin were found significantly reduced using qPCR and WB by sodium restriction (P<0.05), as compared to normal sodium diet. At the opposite, we observed a significant increase in Pecam-1, a specific protein of vascular endothelial cells (P<0.05). Using IF, we detected a co-expression of αSMA and Pecam-1 in 67.3%±4.9 (54 of 88) of cardiac vessels of rats fed normal sodium diet, as compared to 42.3%±3.8 (37 of 88) in rats fed low sodium diet (P<0.05). The transcriptomic study showed that 22 genes, involved in fibrosis, were down-regulated in left ventricles of sodium-restricted rats (P<0.05). By q-PCR, we confirmed that 17 of them were significantly reduced by the low sodium diet (P<0.05). Finally, we established an
in vitro
model of EndoMT, using primary human aortic endothelial (HAoE) cells that were transdifferentiated with TGF-β2 (10ng/ml). We evidenced in HAoE cells the co-expression of Pecam-1 and collagen-1, as a signature of EndoMT. Especially, fibulin 5, one of the genes identified by transcriptomics was found upregulated (13 folds) in the presence of TGF-β2, confirming its potential role in EndoMT. Our study shows that EndoMT is involved in the prevention of cardiac fibrosis by sodium restriction in our rat model of MS. We also confirmed the involvement of ew genes that could be of interest to improve the management of cardiac fibrosis.
Abstract P167: Chronic Circadian Disruption Impairs Cardiovascular Rhythms In Mice
Authors: Pati Paramita , Rhoads Megan K , Meek Rachel , Colson Jackson , Pollock David M , Pollock Jennifer
Published: August 2021

Shift workers have an increased risk of developing hypertension and higher incidence of metabolic syndrome. Circadian rhythm disruption increases cardiometabolic disease risk in humans and animals. We hypothesized that chronic circadian disruption (CCD) disrupts blood pressure, heart rate, and locomotor activity rhythms. Male 8-week old C57BL/6J mice were under a standard light/dark cycle (12-h light, 12-h dark, control) or a CCD protocol (10-h light, 10-h dark, T20) with ad libitum food and water for 10 weeks. T20 mice gained significantly more body weight (n=6, p=0.04; time: p<0.001, light cycle: p<0.001). Mean arterial pressure (MAP), heart rate (HR), and locomotor activity were measured by telemetry after 10 weeks of CCD. Average MAP, HR, and activity were calculated during light and dark periods. MAP between the light and dark periods was significantly different in control mice (12:12 LD), while T20 mice (10:10 LD) did not show diurnal variation (Control 119±3 mm Hg vs.101±2 mm Hg, dark vs. light, respectively, p<0.001; T20 114±13 mm Hg vs.113±12 mm Hg, dark vs. light, respectively, p=0.86; n=3-4 in all groups). Control mice showed a diurnal variation in HR, whereas T20 mice did not show a light-dark difference (Control 584±11 bpm Hg vs. 511±4 bpm, dark vs. light, respectively, p=0.001; T20 537±14 bpm vs. 526±5 bpm, dark vs. light, respectively, p=0.48; n=3-4 in all groups). Dark phase HR was significantly decreased in T20 mice (p=0.01, control dark vs. T20 dark). Control mice showed a light-dark difference in activity, while T20 mice lacked diurnal variation in the activity rhythm (Control 9.6±1.3 counts/min Hg vs. 3.1±0.3 counts/min, dark vs. light, respectively, p<0.001; T20 6.9±0.3 counts/min vs. 6.0±0.8 counts/min, dark vs. light, respectively, p=0.92; n=3-4 in all groups). T20 mice also displayed significantly higher activity during the light phase (p=0.04, control light vs. T20 light). Time of day and the interaction between time of day and light cycle, respectively, were significant between control and T20 mice for MAP, HR, and activity (n=3-4, MAP: p=0.001 and p=0.002; HR: p=0.001 and p=0.004; Activity: p=0.001 and p=0.004). These results indicate that CCD impairs cardiovascular and behavioral rhythms, which may lead to cardiovascular disease.
Abstract P170: Similarities And Differences In The Vascular Impact Of Estrogen Loss Versus G Protein-coupled Estrogen Receptor Deletion
Authors: Kilanowski-Doroh Isabella M , Wong Tristen J , Ogola Benard O , Harris Nicholas , Horton Alec , Laradji Murad , Lindsey Sarah H
Published: August 2021

Women in their postmenopausal years have an increased risk of cardiovascular disease, and recent research suggests that increased vascular stiffness can be detected within a year of the onset of menopause. We have previously demonstrated that the G Protein-Coupled Estrogen Receptor (GPER) protects the vasculature without noticeable changes in blood pressure, but little is known about the underlying structural changes that provide protection. In this study we assessed the impact of estrogen and the G protein-coupled estrogen receptor (GPER) on vascular health, with the hypothesis that loss of estrogen or deletion of smooth muscle cell (smc)-GPER would similarly increase vascular stiffness. Female mice were separated into three cohorts: intact wildtype, ovariectomized (OVX), and GPER smc-KO. OVX occurred at 8 weeks of age and 8 weeks later blood pressure was measured via tail-cuff plethysmography, arterial stiffness was measured as pulse wave velocity (PWV) via high resolution ultrasound, and carotids were excised for biaxial pressure myography and imaging. Uterine weight in OVX mice (0.03 g) was significantly lower than intact mice (0.1 g; p=0.0002) confirming the loss of estrogen. No difference was observed in systolic blood pressure, however, both the OVX (1.5 m/s) and smc-KO (1.9 m/s) groups had significantly higher PWV than intact controls (1.2 m/s; p=0.02 and p=0.03, respectively). Carotids of OVX (366 μm) and smc-KO (389 μm) mice had a smaller outer diameter versus controls (441 μm; p >0.05) without a difference in thickness. Despite the similar responses of OVX and smc-KO groups, Masson’s trichrome staining of carotid sections showed significantly more smooth muscle area fraction in OVX (p=0.005), but not KO mice, and no difference in collagen area fraction. These data indicate that while estrogen loss and smc-KO of GPER both increase arterial stiffness, increased smooth muscle due to estrogen loss is likely not modulated through GPER. Future experiments will aim to understand how other components, such as extracellular matrix genes, may be affected by loss of GPER.
Abstract P171: Comparison Of Modulation Of Renal Arterial Tone By Perivascular Adipose Tissue Between Two Animal Models Of Metabolic Syndrome
Authors: Kagota Satomi , Maruyama-Fumoto Kana , Morikawa Kana , Shinozuka Kazumasa
Published: August 2021

Sex differences have recently been noticed in the regulation of arterial tone by perivascular adipose tissue (PVAT). In SHRSP.Z-

Lepr
fa

/IzmDmcr (SHRSP.ZF) rats, an animal model of metabolic syndrome (MetS), we demonstrated that mesenteric and renal PVAT in female rats consistently have an enhancing effect on vasodilation at 23 weeks, an age by which the effect of PVAT is impaired in the male rats. This could explain the sex differences in the prevalence of cardiovascular complications in patients with MetS. Therefore, we determined whether the sex difference in PVAT response also occurs in another animal model of MetS, SHR/NDmcr-cp (SHR-cp) rats.Renal arteries were isolated from male and female 23-week-old SHR-cp rats, and ring preparations with and without PVAT were made. After a stable contraction was obtained by phenylephrine administration, vasodilation in response to acetylcholine was examined using organ bath methods.Vasodilation in arteries without PVAT from female rats was smaller than that in arteries without PVAT from male rats, and presence of PVAT in arteries from female rats increased vasodilation to the same level as that observed in arteries without PVAT from male rats. Furthermore, renal PVAT in male rats was shown to have an enhancing effect on vasodilation.The present study did not identify sex differences in renal PVAT-mediated modulation in SHR-cp rats because the enhancing effects of PVAT did not disappear in male SHR-cp rats, in contrast to that observed in male SHRSP.ZF rats at the same age. The difference in PVAT response in male rats between two MetS models may be due to differences in the severity of MetS symptoms, especially blood pressure, between the models.
Abstract P172: Impairment Of Estrogen Protective Effect Contributes To Maternal Gestational Hypertension-induced Sensitization Of Hypertensive Response To Post-weaning High Fat Diet In Female Adult Offspring
Authors: Xue Baojian , Yu Yang , Beltz Terry , Guo Fang , Wei Shun-Guang , Pollock Jennifer S , Pollock David M , Johnson Alan K
Published: August 2021

Obesity/high fat diet (HFD) is a risk factor for cardiovascular diseases including hypertension. Recent evidence indicates that maternal gestational hypertension (MGHT) induces hypertensive response sensitization (HTRS) elicited by post-weaning HFD in both male and female offspring. However, the increase in blood pressure (BP) in female offspring is less than that in male offspring. In this study, we investigated if estrogen plays a protective role in MGHT-induced HTRS to post-weaning HFD in female offspring, and if estrogen effects are associated with regulation of brain reactivity to pressor agents and altered autonomic function. In post-weaning HFD fed intact female offspring, MGHT induced HFD-elicited HTRS (MAP, offspring of NT dams, 107.9±0.9 to 115.2±0.7 mmHg; offspring of MGHT dams, 107.3±0.8 to 120.7±1.4 mmHg, p<0.05) and enhanced pressor responses to centrally administered angiotensin (ANG) II (Δ13.7±1.1 mmHg, p<0.05 vs NFD offspring) and tumor necrosis factor α (TNF-α) (Δ13.1±0.7 mmHg, p<0.05 vs NFD offspring). Ovariectomy (OVX) significantly enhanced the HFD-induced increase in BP (115.2±0.7 to 127.1±2.2 mmHg, p<0.05) and the pressor response to central ANG II (Δ11.2±0.9 to Δ18.7±2.3 mmHg, p<0.05) or TNF-α (Δ10.0±1.0 to Δ16.5±1.6 mmHg, p<0.05) in HFD offspring of normotensive (NT) dams. However, MGHT-induced HTRS (MAP, 122.5±1.9 mmHg) and pressor responses to ANG II (Δ16.3±1.0 mmHg) or TNF-α (Δ14.9±1.0 mmHg) in HFD-fed intact offspring of MGHT dams were not potentiated further after OVX when compared to HFD-fed OVX offspring of NT dams. The resting BP and elicited pressor responses remained higher than that of NFD fed offspring of both NT and MGHT dams. Moreover, OVX induced an increase in central nervous system sympathetic drive, and HFD feeding potentiated this effect. The results indicate that estrogen normally plays a protective role in antagonizing HFD prohypertensive effects in offspring of NT dams. MGHT compromises this normal protective action of estrogen to induce HTRS elicited by HFD, which is through augmenting brain reactivity and centrally driven sympathetic activity.
Abstract P173: The Impact Of Cigarette Smoking-oral Contraceptive Combination On Cardiac Remodeling In Premenopausal Female Mice
Authors: Abidi Emna , KAPLAN ABDULLAH , Ghali Rana , Booz George W , Jurjus Abdo , Husari Ahmad , Zouein Fouad
Published: August 2021

Introduction:
Tobacco smoke is a major risk factor for coronary artery diseases (CAD) and chronic tobacco smoking (CS) increase the risk of CAD by 2 to 4 folds. CS effect on cardiac homeostasis has never been evaluated in premenopausal females taking oral contraceptive (OC). This study investigates CS effect on cardiac remodeling in female mice in the presence or absence of Ethinyl Estradiol (EE).

Methods:
Blood pressure and echocardiography were recorded for female C57BL/6J mice on EE, EE-CS, vehicle, and vehicle-CS at baseline and after 8-weeks of exposure. Cardiac inflammatory cytokines and oxidative stress markers were evaluated by real time PCR and western blots. Interstitial collagen deposition was assessed by Masson Trichrome staining.

Results:
Eight weeks of EE-CS treated mice showed no effect on BP but significant adverse structural and functional cardiac effects, represented by increased systolic (0.981 ± 0.035 N=11 (p<0.0332)) and diastolic (1.450 ± 0.037 N=11 (p<0.0002)) areas when compared to the vehicle and EE groups, along with increased systolic (1.981 ± 0.109 N=11 (p<0.033)) and diastolic ( 3.911 ± 0.159 N=11 (p<0.033)) volumes when compared to all groups. Functional changes were accompanied with a decreased fractional shortening (9.194 ± 1.006 N=11 (p<0.033)) when compared to vehicle and EE groups with no changes in ejection fraction parameter. Moreover EE-CS treatment significantly increased NOX-4 expression (2.297 ± 0.643 N=5 (p<0.033)) when compared to EE treatment alone, along with an increased pro-inflammatory profile including IL-1β (0.750 ±0.171N=5 (p<0.033)) and IL-4 (4.110 ± 0.623 N= 5 (p<0.002)) when compared to all groups, and IL-6 (3.045±0.910 N=5 (p<0.002)) and IL-13 (2.686 ± 0.648 N=5 (p<0.033)) when compared to vehicle-CS group. Morphologically, EE-CS exhibited a significant increase in interstitial fibrosis (1.186± 0.020 N=5, 3.2285 ± 0.683 N=5, (p<0.033)) when compared to the vehicle-CS group.

Conclusion:
This study provides clear evidence that CS-exposed premenopausal female mice on OC regimen exhibited significant adverse cardiac events that could be classified under cardiac dysfunction with preserved ejection fraction. Additional experiments are warranted to further elaborate on these findings.
Abstract P177: Sex- And Strain- Specific Metabolic Effects Of Postnatal Bpf Exposure In Heterogeneous Stock Rat Founding Inbred Strains
Authors: Wagner Valerie A , Clark Karen C , Holl Katie L , Reho John J , Grobe Justin L , Kwitek Anne E
Published: August 2021

Bisphenol F (BPF) is increasing substituting bisphenol A (BPA), an endocrine disruptor associated with cardiometabolic disease, in manufacturing polycarbonates and consumer products. Interindividual variation in bisphenol levels suggests that gene x environment (GxE) interactions influence cardiometabolic disease risk from bisphenol exposure. Studies show that BPF is a potent endocrine disruptor with effects on thyroid, reproductive health, and neuroendocrine functions. Traditional
in vivo
toxicity studies are performed in isogenic or genetically undefined outbred rodents, leading to conflicting results possibly due to GxE interactions. The N/NIH Heterogeneous Stock (HS) rats are a genetically heterogeneous population amenable to genetic study. Our overall study hypothesis is that BPF-induced cardiometabolic disease has underlying genetic risk, which can be identified using the HS rat and its founding inbred strains. We previously demonstrated that five weeks of postnatal BPF exposure significantly impacts body growth and adiposity in male HS rats. The goal of this project was to evaluate the metabolic health impact of postnatal BPF exposure in HS founding inbred strains. Weanling littermate pairs of male and female ACI/EurMcwi (ACI), BN/NHsdMcwi (BN), F344/Stm (F344), and WKY/NCrl (WKY) rats were randomly exposed to either vehicle (0.1% EtOH) or 1.125 mg BPF/L in 0.1% EtOH for ten weeks in drinking water. Cardiometabolic measures, tissues, urine, and feces were taken. Our studies determined BPF exposure in ACI female rats significantly increased feeding efficiency (0.54 ± 0.07 vs 0.62 ± 0.06 vs, p=0.04), suggesting a possible decrease in metabolic rate. BPF exposure impacted males more often than females, with ACI males showing significantly increased thyroid mass (0.045 ± 0.004 mg/g vs 0.051 ± 0.003 mg/g, p<0.01), BN males showing a trend in increased pituitary mass (0.026 ± 0.003 mg/g vs 0.029 ± 0.001 mg/g, p=0.07), and WKY males showing increased adrenal mass (0.164 ± 0.010 mg/g vs 0.176 ± 0.005 mg/g, p<0.01). Our preliminary data suggests that the ACI strain and male BN and WKY are susceptible to metabolic effects of BPF exposure. This work indicates that the HS rat will be a useful model for dissecting GxBPF interactions on metabolic health.
Abstract P179: Explaining The Increase Of Hypertension Prevalence In Bangladesh From 2011 To 2018: Evidence From National Surveys
Authors: RANA Juwel , Islam Rakibul
Published: August 2021

Objective:
General trends in the epidemiology of hypertension are best described by studying the same population over time, but studies are limited. Using surveys from Bangladesh in 2011 and 2017-18, we examined i) the change in the prevalence of hypertension, ii) the extent to which changes in traditional hypertension risk factors explained the increase, and iii) the change in the distribution of systolic and diastolic blood pressure over time.

Methods:
Two independent Bangladesh Demographic and Health Surveys were undertaken in 2011 and 2017-18 using similar methodology in adults aged 35 years and older. Hypertension was defined as having systolic blood pressure (SBP) ≥140 mmHg and/or a diastolic blood pressure (DBP) ≥90 mmHg and/or taking antihypertensive drugs to control blood pressure. Age-standardized prevalence of hypertension was estimated with direct standardization using population census 2011, and a multilevel mixed-effects Poisson regression model with robust variance was used to explain the increase of hypertension from 2011 to 2018.

Results:
The age-standardized prevalence of hypertension in 2017-18 was 43.4% (95% CI 40.2-46.6) in men and 53.4% (95% CI 50.8-56.0) in women, representing an increase since 2011 of 54% and 8% in men and women, respectively. The age, body mass index, education, and diabetes explained the increase in the prevalence of hypertension from 2011 to 2017-18. We observed statistically significant sex-differences in the increase of hypertension in 2018 (p-difference <0.0001). Increases in SBP and DBP were also seen across the population over the period.

Conclusions:
In Bangladesh, there has been a marked increase in hypertension prevalence over seven years, especially in men. This largely results from changes in traditional risk factors, leading to population-wide increases in blood pressure levels. Interventions to control this exacerbation of hypertension should focus on population-wide strategies.
Abstract P182: Microangiopathic Complications In Malignant Hypertension: An Under-appreciated Form Of Target Organ Damage
Authors: Jain Akhil , Singhal Bhumika , Jindal Rishabh , Jani Chinmay , Gupta Puneet K
Published: August 2021

Fig 1: Summary of Malignant Hypertension Studies having Microangiopathic Complications along with Forest Plot Microangiopathic Complications in Malignant Hypertension: An underappreciated form of Target Organ Damage

Background:
Renal thrombotic microangiopathy is a clinically important complication of malignant hypertension (MHT), but its incidence in MHT has been sparsely studied. Our aim was to study the incidence of microangiopathic changes (MaC) in MHT.

Methods:
We searched Google Scholar database studies directly reporting MaC (mentioning either microangiopathic hemolytic anemia or thrombotic angiopathy) in presence of MHT. We used OpenMeta[Analyst] for the pooled analysis.

Results:
From 1967 to 2019, 9 studies were included. Maximum likelihood random-effects method showed pooled proportion estimate of having MaC in MHT to be 0.4 (95 CI: 0.3, 0.5; p<0.1). Significant heterogeneity with I
2
=82.56%, p <0.1 was found. Subgroup analysis showed pooled proportion of MaC in MHT to be 0.5 (95 CI: 0.4,0.7, p<0.1) for studies before 2000; whereas 0.2 (95 CI: 0.2, 0.3, p<0.1) for studies after 2000. Sex-wise distribution was reported in 7 studies, risk ratio of having MaC in MHT in female was found to be 1.24 compared to male.

Conclusion:
Our analysis suggests decreasing incidence of MaC in MHT over the past couple of decades and increased risk of this complication in females, although significant heterogeneity exists among studies reporting microangiopathic changes in malignant hypertension. More prospective observational studies are needed to better define the epidemiology of the hematological changes that occur in MHT since they have important therapeutic implications.
Abstract P183: Effects Of L-arginine Supplementation On Cognitive Impairment In Hypertensive Frail Elderly Adults
Authors: Mone Pasquale , Gambardella Jessica , Pansini Antonella , Rizzo Mario , Frullone Salvatore , Santulli Gaetano
Published: August 2021

Background:
L-Arginine is an amino acid which is involved in nitric oxide production regulating vascular tone and cardiovascular homeostasis. Hypertension is one of the most common comorbidities worldwide, and leads to endothelial dysfunction contributing to atherosclerosis, inflammation, and oxidative stress. Frailty is a syndrome of decreased physiological reserves with increased susceptibility to stressors leading to higher mortality, hospitalization, disability, and functional and cognitive impairment. Cognitive impairment is a very common feature in hypertensive frail older adults. Hence, it is very important to treat cognitive impairment to delay and/or prevent adverse events. Our study, thus, investigated the effects of 4-weeks supplementation of L-Arginine on global cognitive function.

Methods:
We studied 101 frail older patients from April 2020 to April 2021. All subjects were recruited from ASL (local health company of Italian Ministry of Health) Avellino, Italy. All patients fulfilled all of the following inclusion criteria: a previous diagnosis of hypertension, a confirmed frail status, age >65 years. The exclusion criteria were: age <65 years, absence of frailty status, absence of hypertension, left ventricular ejection fraction <25%, with previous myocardial infarction or previous PPCI or/and coronary by-pass grafting, or previous fibrinolytic therapy. The study was approved by the local Ethics Committee and a written consent was signed.

Results:
We are reporting here the results in 52 patients who hitherto successfully completed the study. The cognitive screening was available at baseline (before treatment) and during a follow-up of 4 weeks. The non-treated group (n=27) had a Montreal Cognitive Assessment (MoCA) score 22.9±0.9 at basal and 23.4±1.0 at follow-up (p=0.06). The treated group (oral L-Arginine, 1.66 g, twice a day; n=25) displayed a MoCA score 23.1±0.7 at basal and 24.2±0.6 at follow-up (p<0.001); the difference between the follow-up groups was significant as well (p<0.001).

Conclusions:
Our data show a significant improvement in the MoCA score in the group treated with L-Arginine. More extensive studies are needed to verify the efficacy of L-Arginine in this population.
Abstract P185: Racial Disparities In The Influence Of Endocrine-Disrupting Chemicals On Hypertension-Related Mortality In The US Adult Population
Authors: Banerjee Srikanta , Huth John
Published: August 2021

Bisphenol A (BPA) is an endocrine-disruptive chemical derived from plastics and epoxies which have been linked to atherosclerosis and obesity. Cardiovascular disease (CVD) also disproportionately affects minority populations. Among environmental toxins, Black Americans are found to have higher BPA levels than the general population. In this study, we assessed the hypothesis that if BPA leads to higher mortality outcomes among individuals with hypertension only in Non-Hispanic Black Americans.From the 2003-2010 National Health and Nutrition Examination Survey, we analyzed data on adults (≥ 20 years), with mortality data obtained through 2015. Hypertension status was determined from medication usage information and self-report status. The causes of death for adults (N=3407) were defined using the International Classification of Disease coding (ICD-10). Urinary BPA levels were considered elevated at ≥1.97 μg/g. Complex Samples Cox Regression was used to assess if BPA levels influence the effect of hypertension on mortality and if this pattern persists across races. Out of the Non-Hispanic Black respondents, 10.5% of males died from hypertension versus 13.1% of females. During the 8.6-year follow-up, the unadjusted hazard ratio (HR) of hypertension to no hypertension for Non-Hispanic Black Adults was 3.22; 95% confidence interval [CI: 2.19-4.75]. The adjusted HR was elevated, 2.98 (CI 1.19-7.46, p = 0.02), among BPA-exposed individuals but closer to 1.0 (1.08 CI 0.45-2.59, p = 0.87) among unexposed individuals, after controlling for medical and demographic risk factors. However, among Non-Hispanic White individuals, increased BPA levels did not significantly influence mortality in those individuals with hypertension. In conclusion, there was increased mortality outcomes among BPA-exposed, Non-Hispanic Black individuals experiencing hypertension than those individuals without hypertension. Due to the chronicity of exposure among environmental hazards, social disparities are compounded over a long period of time. Environmental exposures like BPA should be monitored especially among vulnerable populations and thereby improve hypertension related health outcomes.
Abstract P189: AT
1
R-Dependent Blood-Brain Barrier Disruption Precedes Neuroinflammation In Age-Dependent Hypertension
Authors: Nist Kayla M , Moreira Jesse , Wainford Richard D
Published: August 2021

AIM:
We hypothesized paraventricular nucleus (PVN)-specific blood-brain barrier (BBB) dysfunction and neuroinflammation contribute to hypertension and sympathoexcitation that can be attenuated by an Angiotensin II Type 1 Receptor (AT
1
R)-dependent mechanism in the aging Sprague-Dawley (SD) rat.

Methods:
Naïve male SD rats aged 3-, 8- and 16-months-old (MO) (N=4-6/gp) were used in the following studies. Separate groups of 16 MO rats were administered losartan (21 days; s.c. 3 mg/kg/day) or hydrochlorothiazide (14 days; s.c. 4 mg/kg/day). Blood pressure (femoral cannulation) and plasma NE (ELISA) were assessed at end of study. In separate groups, BBB dysfunction was assessed via PVN FITC extravasation using intravascular co-infusion of FITC-Dextran (10 kDa) and rhodamine B isothiocyanate-Dextran (70 kDa). IHC/IF was performed in naive and losartan-treated rats for microglia (CD11b/c) and astrocytes (GFAP) in the PVN and subfornical organ (SFO).

Results:
Male SD rats develop HTN and sympathoexcitation with age. At 8 and 16 MO, rats exhibit PVN BBB dysfunction (increased FITC extravasation). However, only 16 MO rats exhibit significant PVN neuroinflammation (increased microglial activation and astrocyte reactivity). In the SFO, there is no evidence of age-dependent neuroinflammation. Losartan and HCTZ both significantly lower blood pressure to similar levels, however, only losartan significantly attenuates PVN BBB dysfunction and neuroinflammation.

Conclusions:
Within the PVN, a known neural control center, there are AT
1
R-dependent increases in PVN BBB disruption and neuroinflammation that we speculate contribute to hypertension in aging SD rats.
Abstract P192: Orthostatic Tolerance Before And After 60 Days Of Strict Head Down Tilt Bedrest With And Without Daily Artificial Gravity Training
Authors: Hoenemann Jan , Hoffmann Fabian , Moestl Stefan , Heusser Karten , Mulder Edwin , van Herwaarden Teun , Lee Stuart , Jordan Jens , Tank Jens
Published: August 2021

Background:
Orthostatic intolerance occurs after space flight, immobilization and in patients with autonomic diseases, so there is a need for more effective countermeasures. We hypothesized that daily artificial gravity elicited through short-arm centrifugation attenuates plasma volume loss and orthostatic intolerance following 60 days of HDTBR, which models cardiovascular responses to weightlessness.

Methods:
We studied 24 healthy persons (8 women, 33.4±9.3 yr, 24.3±2.1 kg/m2) exposed to 60d HDTBR. Subjects were assigned to 30 min/d continuous short arm centrifugation (cAG), 6x5 min short arm centrifugation (iAG), or a control group (ctr, no countermeasures). Head-up tilt testing (15 min of 80°) followed by incremental lower body negative pressure (-10 mmHg every 3 min) until presyncope was performed before and at the end of HDTBR. Plasma volume was measured (CO rebreathing) 12-2 days before and after 56d of HDTBR. Stroke volume was measured by cMRI. Norepinephrine, epinephrine, aldosterone, and renine plasma levels were measured before and after HDTBR.

Results:
Time to presyncope decreased in all groups following bedrest (ctr: 22:56 min pre and 9:35 min post, cAG 15:34 min pre and 10:11 min post; iAG 14:56 min pre and 10:00 min post, p<0.001). The significant interaction (p=0.025) between bedrest and intervention was explained by greater baseline orthostatic tolerance time in the ctr. AG Data was pooled analysis. The reduction in stroke volume (ctr, pre: 93±19 ml, HDTBR: 69±13 ml, AG, pre: 88±20 ml, HDTBR: 67±17 ml) and plasma volume was similar (ctr, pre: 4155±1085 ml, HDTBR: 3855±1087 ml, AG, pre: 4114±1250 ml, HDTBR: 3674± 1313 ml). Catechols and aldosterone did not change significantly during bedrest. The increase in renine was similar between groups (ctr pre: 18±12 mE/L, HDTBR: 21±8 mE/L, AG pre: 21±10 mE/L, HDTBR: 31±12 mE/L).

Conclusions:
30 min daily AG didn’t prevent a reduction in orthostatic tolerance following 60d HDTBR. Whether numerically smaller reductions in orthostatic tolerance in the AG groups indicate efficacy or result from baseline differences can’t be ascertained. A stronger AG stimulus or combination with other countermeasures might be required to maintain orthostatic tolerance and to attenuate the volume reduction.
Abstract P201: Negative Regulation Of PVN Pre-sympathetic Neuronal Activity By Resident Microglia
Authors: Shi Peng , Lin Yunfan , Bi Qianqian , Cheng Guo , Shen Xiao
Published: August 2021

Hypothalamic paraventricular nucleus (PVN) is a critical integrating region in controlling peripheral sympathetic tonicity. While the vast studies have unraveled the regulatory circuits affecting PVN pre-sympathetic neurons, local factors for maintaining the homeostasis of neuronal excitability are barely understood. In the present study we investigated the role of microglia, the primary resident immune cells of the CNS, in this context. By electrophysiological recording, we found that loss of resident microglia induced an increased firing frequency and attenuated outward potassium currents in the PVN pre-sympathetic neurons, tachycardia and impaired heart rate variability. Combining the transcriptomics analysis of the PVN microglia, we identified a releasable factor, which was dominantly expressed in microglia compared to other brain parenchymal cells. ICV infusion of the recombinant peptide restored potassium currents in the PVN pre-sympathetic neurons and autonomic function in microglia-depleted mice. In summary, our results provided a novel intrinsic regulatory mechanism by which microglia suppress neuronal over excitation in physiological condition.
Abstract P206: Improvement Of Autonomic Function, Sleep, Depression, Anxiety, And Stress In Military Personnel With Traumatic Stress After Use Of A Closed Loop Neurotechnology
Authors: Tegeler Catherine , Howard Lindsay , Brown Kenzie L , Asif-Fraz Faiza , Kellar Dawn C , Shaltout Hossam A , Tegeler Charles H
Published: August 2021

Introduction:
Symptoms associated with military-related traumatic stress (MTS) include insomnia, depression, anxiety, and impaired autonomic control. High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM®) is a noninvasive, closed-loop acoustic stimulation technology that identifies dominant brain frequencies and translates them in real time into audible tones of variable pitch and timing, to support self-optimization of brain activity.

Objective:
Evaluate changes in autonomic and symptoms scores after use of HIRREM in subjects enrolled in a pilot study for MTS.

Methods:
Thirty-two service members or Veterans (1 female), mean (SD) age 40.8 (6.4), with MTS symptoms for 7.3 years (3.9), received 19.2 (1.0) HIRREM sessions over 12 days. Continuous recordings of blood pressure and heart rate, for analysis of baroreflex sensitivity (BRS) and heart rate variability (HRV), were done at V1 and V2. Symptom inventories collected before (Visit 1, V1), immediately after (primary outcome, V2, n = 32), and at 1, 3, and 6 months after completion of HIRREM included traumatic stress (PCL-M), insomnia (ISI), depression (CES-D), and anxiety (GAD-7). Paired t-tests were performed.

Results:
HIRREM improved BRS measured as HF alpha (10.8 ms/mmHg, 2.5, p<0.001), Sequence Down (7.3 ms/mmHg, 2.1, p<0.001), Sequence Up (7.6 ms/mmHg, 2.4, p=0.001), and Sequence All (7.3 ms/mmHg, 1.8, p<0.001), as well as HRV; SDNN (14.1 ms, 3.6, p=0.005), rMSSD (12.8 ms, 2.6, p<0.05). MAP dropped 2.7 mmHg, 1.2, p<0.05 and SAP dropped 5.9 mmHg, 1.8, p=0.007. Mean symptom scores were reduced at V2; PCL-M [-12.9 (± 9.1), p<0.001], ISI [-6.3 (± 5.0), p<0.001], CES-D [-13.7 (±9.2), p<0.001], and GAD-7 [-6.7. (± 4.7), p<0.001]. Symptom scores improved 1-month post-HIRREM for all measures, and clinically relevant and significant benefits persist at 3 and 6 months.

Conclusions:
These results suggest improved autonomic cardiovascular regulation and statistically significant reduction in scales associated with the use of HIRREM for symptoms of MTS. Controlled trials could provide important insights regarding both the mechanisms associated with the beneficial effects of HIRREM, and the functional disturbances underlying MTS.
Abstract P214: Isolevuglandins Mediate Inflammatory Gene Expression And Immune Activation In Hypertension And Systemic Lupus Erythematosus
Authors: de la Visitacion Nestor , Smart Charles D , Krishnan Jaya , Harrison David G , Patrick David M
Published: August 2021

Justification:
Hypertension and systemic lupus erythematosus (SLE) share similarities including elevations of blood pressure, proteinuria, inflammation and renal dysfunction and both involve formation of isoLG adducts. We hypothesized that isoLG scavenging would modulate overlapping gene pathways in inflammatory cells in these two conditions.

Methods:
We performed 10 X genomics single cell sequencing on splenocytes of C57Bl/6 mice with angiotensin II (Ang II)-induced hypertension, Ang II co-treatment with the isoLG scavenger 2HOBA, and 24-week-old B6.SLE123 mice with or without 6-weeks of 2HOBA. Matched C57Bl/6 females were used as controls for the B6.SLE123 mice.

Results:
Both models exhibited myeloid expansion and genes associated with neutrophil infiltration compared to their respective controls and 2HOBA attenuated this (
Table 1
). Hypertension was associated with neutrophil expansion whereas SLE was associated an expansion of neutrophils, monocytes, and dendritic cells. In SLE, 2HOBA predominantly modulated gene expression in dendritic cells. Gene ontology revealed 2HOBA downregulated genes governing inflammation including
Il1
β
(Avglog2(fold change) = -1.6, P
adj
= 0.002) in both hypertension and SLE.

Conclusions:
In a mouse model of SLE, scavenging of isoLGs with 2HOBA downregulates inflammatory genes specifically in DCs. In models of both hypertension and SLE, scavenging of isoLG prevents neutrophil expansion. Combined these data describe a shared role of isoLGs in hypertension and SLE and suggest a specific role of DCs and neutrophil activation in the pathogenesis of both conditions.

Table 1.

Percentage of myeloid derived cells in all groups.
Abstract P230: Prevention Of Maternal Obesity Attenuates Adverse Offspring Cardiometabolic Outcomes In Preeclamptic-like Mouse Model
Authors: Beckers Kalie , Flanagan Juliet , Gomes Viviane , Liu ChinCHi , Johnston Andrea , Sones Jennifer L
Published: August 2021

Preeclampsia (PE) is a hypertensive disorder of pregnancy and a leading cause of maternal and fetal mortality with maternal obesity as a risk factor. Decreasing white adipose tissue (WAT) via calorie restriction during the first half of pregnancy may alter the maternal-fetal environment to improve offspring outcomes. We hypothesized that pair-feeding BPH/5 dams during pregnancy will improve cardiometabolic risk and WAT pro-inflammatory cytokine expression in BPH/5 offspring in a sex-dependent manner. Previously, we showed that BPH/5 males, unlike females, have similar body weights, daily food intake, and circulating leptin levels as compared to age-matched control mice. Although, adult BPH/5 females and males have cardiomegaly and increased subcutaneous and peri-renal WAT mass compared to lean control mice. To investigate the prevention of maternal obesity on offspring outcomes, BPH/5 dams were pair-fed (PF) beginning at embryonic day (e)0.5 to C57 pregnant mice. Offspring cardiometabolic risk and WAT pro-inflammatory cytokine mRNA were measured using real time PCR in adult ad libitum fed offspring. Compared to controls, peri-renal WAT from BPH/5 males showed a 5-fold increase while females had a 15-fold increase in TNFa (n=3-6; p<0.05), 6-fold increase in PTGS-2 for males and 5-fold increase for females (n=3-6; p<0.05), and 3-fold increase in IL-6 for males and 1.25-fold increase for females (n=3-6; p<0.05) in subcutaneous WAT. Adult offspring born to PF BPH/5 dams had decreased expression in TNFa (male: 4-fold and female: 7-fold), PTGS-2 (male: 5-fold and female: 4-fold), and IL-6 (male: 10-fold; n=3-6; p<0.05). In conclusion, prevention of maternal obesity in BPH/5 dams attenuates cardiometabolic risks and reduces the pro-inflammatory WAT milieu in male and female offspring. The transgenerational effects during pregnancy is believed to be caused by an alteration in the maternal-fetal environment due to WAT pro-inflammatory adipokines. Future investigations are necessary to understand the differences observed in BPH/5 male versus female mice into adulthood as well as the transgenerational impact of attenuated maternal obesity in pregnancy.
Abstract P232: Pregnancy Induced Changes In Urinary Uromodulin Excretion In Normotensive And Chronic Hypertensive Rodent Models
Authors: Mary Sheon , Boder Philipp , Graham Delyth , Delles Christian
Published: August 2021

Hypertensive disorders complicate 1-4% of pregnancies and are the leading cause of maternal death. Pregnancy involves major adaptions in renal hemodynamics, tubular and endocrine functions. Uromodulin (UMOD) is a renal protein that plays a role in renal sodium and divalent cation transport and is associated with hypertension and kidney diseases. We aimed to understand the role of blood pressure (BP) in urinary UMOD excretion during pregnancy. Pregnant Wistar Kyoto (WKY) and Stroke Prone Spontaneously Hypertensive (SHRSP) rats (n=8) were studied for 18.5 gestational days (GD). A group of pregnant SHRSP were treated with the beta-blocker propranolol (100mg/kgBW/day; n=8) and the calcium channel blocker nifedipine (25mg/kgBW/day; n=7) from GD 0.5. Systolic BP (SBP; tail cuff plethysmography), urine and plasma characteristic were monitored at baseline, GD3.5, GD12.5 and GD 18.5. UMOD concentration were measured in 24hr urine with ELISA. Pregnant SHRSP were hypertensive throughout the gestation compared to WKY (delta SBP 22.6 ± 3.6 mmHg, p<0.0001). At baseline (pre-pregnancy), urinary UMOD levels were 2-fold higher in WKY compared to SHRSP (p<0.05). During pregnancy, the urinary UMOD gradually decreased in WKY (2-fold decrease, p<0.05), whereas a 1.5-fold increase (p<0.05) was observed in hypertensive SHRSP compared to pre-pregnancy. The changes observed in urinary levels corresponded to total kidney UMOD levels at GD18.5, wherein SHRSP kidney shows 1.3-fold (p<0.01) greater expression of UMOD compared to WKY. Nifedipine reduced BP in pregnant SHRSP (delta SBP between GD18.5 and baseline: 44.3 ± 7.4 mmHg, p<0.0001) while propranolol did not affect BP. However, neither nifedipine nor propranolol changed urinary UMOD excretion in pregnant SHRSP. BP was not significantly correlated with urinary uromodulin levels in pregnant WKY (Pearson, r=-0.01, p 0.95) and SHRSP without (r=-0.16, p 0.46) or with (nifedipine r=0.26, p 0.31; propranolol r=0.17, p 0.45) antihypertensive treatment. We demonstrate differences in UMOD excretion between hypertensive and normotensive pregnancy and changes during pregnancy that are at least in part BP independent. Our data provide novel insights into molecular changes associated with hypertensive pregnancy.