bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 59: Beclin-1-Dependent Autophagy Prevents Hyperaldosternism-Induced Endothelial Dysfunction And Hypertension
Authors: Costa Rafael , Bruder Nascimento Ariane , Tostes Rita , Bruder Thiago
Published: October 2024

Hyperaldosteronism (HA), characterized by the overproduction of aldosterone (Aldo), leads to cardiovascular damage, including endothelial dysfunction. Beclin-1 (Becn1) is a key protein regulating autophagy, a recycling process for unwanted components. Whether HA disturbs autophagic flux in endothelial cells via Becn1 is unknown. We hypothesize that Becn1-dependent autophagic flux will improve endothelial function and inhibit the hypertension (HTN) in HA. 10-to-12-week-old male C57BL/6J (WT) or Becn1 knock-in mice (Becn1
Tg
) were infused with aldosterone for 14 days (600 µg/kg/day). Vascular function was studied in mesenteric arteries (MA) and blood pressure was analyzed by radiotelemetry. HA disrupted MA autophagic flux characterized by accumulation of LC3A/B and p62 and reduction in Becn1 expression and activity followed by suppressed acetylcholine (ACh)-induced vasodilation (% relaxation) in WT [WT: 91.5±1.1
vs
HA: 56.7±2.7], whereas Becn1
Tg
mice were protected from HA-induced HTN [mean blood pressure (mmHg) – WT_Aldo: 149.1±1.2
vs
BCN1_Aldo: 118.1±0.8] and endothelial dysfunction [HA_Becn1
Tg
: 92.8±2.9]. Given the link between the immune system and cardiovascular diseases, we investigated whether HA reduces autophagic flux and BCN1 in immune cells. HA led to the accumulation of LC3A/B and p62, and decreased BCN1 activity in peritoneal cavity cells of WT mice, however bone marrow transplant from Becn1
Tg
mice into WT mice did not confer protection against HA-induced changes in vascular reactivity [WT to WT_HA: 51.2±1.3
vs
Becn1
Tg
to WT_HA: 53.8±1.9]. As a pharmacological approach, we accelerated autophagic flux by treating mice with spermidine (3 mM for 7 days), which subsequently improved endothelial function in HA [HA: 52.7±3.9
vs
HA+spermidine: 88.9±3.9]. To assess the direct impact of Aldo on disrupting autophagy flux in endothelial cells, we treated mesenteric endothelial cells (MEC) with Aldo (0.1 µM for 24 hours). This treatment resulted in the accumulation of LC3A/B and p62 proteins and a reduction in BCN1 activity, accompanied by an upregulation in the mRNA expression of pro-inflammatory cytokines. All these effects were prevented by spermidine (100 uM for 3h). These findings reveal a novel pathway in HA-associated endothelial dysfunction and HTN, where Aldo disrupts autophagic flux and inflammation by suppressing BCN1 activity, positioning BCN1 as a pharmacological target for cardiovascular outcomes in HA.
Abstract 69: Female Blood Pressure High 5 Mice Display Cerebral Hypoperfusion In the Non-Pregnant and Late Pregnant State
Authors: Darden Chauncey , Saffold Karen , Shao Qingmei , Rouser Shanise , Spradley Frank , Warrington Junie
Published: October 2024

The rates of hypertensive pregnancy disorders such as gestational hypertension, pre-eclampsia/eclampsia (PE/E), and chronic hypertension with or without superimposed PE have increased in recent years. Cerebrovascular disorders in the antenatal and postpartum period are common complications of hypertensive pregnancy disorders. Chronic hypertension is linked to cerebrovascular rarefaction, decreased regional perfusion, and cognitive decline later in life. The blood pressure high 5 (BPH/5) mouse has been characterized as a model of superimposed PE; however, cerebrovascular changes have not been described. We hypothesized that BPH/5 mice will display reduced regional cerebral perfusion regardless of pregnancy status. To test this, we used non-pregnant and timed-pregnant BPH5 mice and control SMA-GFP mice (C57/BL6 background) (n=3-4 per group). On gestational day 18.5, cerebral perfusion was measured using laser speckle imaging in different brain regions, along with general physiological characteristics (heart rate and oxygen saturation), body, heart, and brain weight, and the number and weight of live fetuses. There was a main effect of pregnancy to increase body weight (p<0.01), hematocrit (p=0.04), and sPO2 (p=0.02). There was a strain effect on sPO2 (p<0.01), heart rate (p<0.01), perfusion of right parietal cortex (p=0.02), whole brain (p<0.01), prefrontal cortex (p<0.01), with significant decreases in pregnant BPH5 compared to pregnant SMA-GFP mice (p<0.05). There was no difference in number (8±1 vs 6±2) and mean body weight (1021±24 vs 883±160 mg) of live fetuses between control vs. BPH5 mice (Mean ± SD). These results support the hypothesis chronic hypertension and superimposed PE lead to reduced cerebral perfusion. Future studies will determine whether reduced cerebral perfusion is associated with cerebrovascular rarefaction and whether these are blood pressure dependent.
Abstract MP09: Characteristics of Antihypertension Medication Adherence Among Patients with Resistant Hypertension in the RADIANCE HTN-TRIO Ultrasound Renal Denervation Trial
Authors: Azizi Michel , Kirtane Ajay , Bloch Michael , Kably Benjamin , Weil Joachim , Thompson Georgia , McGuire Maureen , McClure Candace K , Fisher Naomi
Published: October 2024

Background:
About 50% of patients are nonadherent to antihypertensive medications (AHM), impairing blood pressure (BP) management. The RADIANCE-HTN TRIO trial screened patients with resistant hypertension by first placing them on a fixed-dose combination triple pill (ARB+amlodipine+HCTZ). Ambulatory BP measurement 4 weeks later found 43% had controlled BP and were thus ineligible for enrollment. A total of 136 patients with uncontrolled BP were randomized to ultrasound renal denervation (uRDN) or sham-control. This analysis assessed adherence characteristics among patients in the trial.

Method:
TRIO patients consented to have chemical adherence testing that detected AHM or their metabolites in spot urine samples at baseline, 2 and 6 months. Full adherence (FA) was defined by all prescribed drugs detected in the sample.

Results:
Adherence data were available at any timepoint for 129 and all timepoints for 91 patients. Among patients with data at all timepoints, 66% (60/91) were FA and 34% (31/91) were partially- or fully nonadherent (PA/NA) to any of their prescribed medications. Adherence rates did not differ between treatment groups or geographies. Women were less likely to be FA (p<0.001) (Table). PA/NA patients had higher rates of peripheral and cerebrovascular disease, and higher BP before and after triple pill. Adherence to triple pill was 81% at baseline, 85% at 2-months, and 83% at 6-months. Medications were titrated after 2-months. At 6-months, adherence to additional medication classes prescribed was: aldosterone antagonist 71%, beta blockers 62%, and centrally-acting alpha-2 agonists 60%.

Conclusions:
The stringent TRIO study design uncovered significant medication nonadherence that translated into a high rate of apparent resistant HTN. It also showed high adherence to a fixed-dose triple pill. One third of enrolled patients were not fully adherent to medications, and these patients had higher BP and higher rates of vascular disease. Understanding clinical features associated with medication adherence may improve hypertension management.
Abstract MP22: Association between 2,5-dimethylfuran exposure and the risk of early-onset hypertension: evidence from NHANES data
Authors: Ge Chenliang
Published: October 2024

Objective:
This study aimed to investigate the relationship between exposure to volatile organic compounds (VOCs) and the prevalence of early-onset hypertension (EHT) within the US population.

Methods:
Data from the National Health and Nutrition Examination Survey (NHANES) was utilized for this cross-sectional analysis. Weighted logistic regression models, adjusted for potential confounding variables, were employed to determine the association between blood VOC concentrations and EHT prevalence. The combined impact of exposure to multiple VOCs was assessed using weighted quantile sum (WQS) regression analysis.

Results:
Statistically significant, independent associations were observed between elevated blood VOC concentrations and increased EHT prevalence. Each unit increase in the WQS index was associated with a 91% increased risk of EHT (Odds Ratio [OR]: 1.82, 95% Confidence Interval [CI]: 1.54-2.16, P < 0.01). Among the VOCs studied, 2,5-dimethylfuran demonstrated the highest weight in the WQS model. Restricted cubic spline analysis revealed a linear, positive correlation between blood 2,5-dimethylfuran levels and EHT probability, with the risk of EHT increasing by 37% (OR: 1.37, 95% CI: 1.18-1.59) for each additional unit (10
-1
ng/mL) of 2,5-dimethylfuran. This association between 2,5-dimethylfuran exposure and EHT remained consistent across various statistical models and demographic subgroups, with more pronounced effects observed in individuals with lower body mass index and smokers.

Conclusion:
This study highlights the potential role of 2,5-dimethylfuran exposure in the development of EHT. These findings emphasize the need to consider 2,5-dimethylfuran exposure in public health initiatives aimed at mitigating the rising prevalence of EHT. Further research is warranted to elucidate the underlying mechanisms of this association and investigate the long-term health consequences of 2,5-dimethylfuran exposure in young adults.
Abstract MP27: Pregnant Women of Advanced Maternal Age Have Higher Central Artery Stiffness Than Younger Pregnant Women
Authors: Lee Ruda , Santillan Mark , Santillan Donna , Stroud Amy , Nuckols Virginia , Dubose Lyndsey , Brandt Debra , Stanhewicz Anna , Pierce Gary
Published: October 2024

The frequency of women undergoing pregnancy at advanced maternal age (AMA, ≥35 years) is increasing in developed countries, including the United States. AMA is associated with an increased risk of adverse pregnancy outcomes such as gestational hypertension, preeclampsia, and preterm birth. Increased risk for adverse pregnancy outcomes at AMA may be mediated in part by altered arterial structure and function or inadequate maternal arterial adaptations during pregnancy. Therefore, we examined central artery stiffness and endothelial function across healthy pregnancy (i.e. no comorbid maternal or fetal conditions, born at term) in women who had enrolled in a longitudinal study between March 2015 and January 2020. We hypothesized that women at AMA (age ≥35 years, mean±SE: 36±0 years, n=18) would have higher arterial stiffness and lower endothelial function compared with younger women (age 21-30 years, mean±SE: 27±0 years, n=51) across pregnancy. Hemodynamic and arterial function measures were collected in the first (6-13 weeks), second (18-26 weeks), and third (27-37 weeks) trimesters and postpartum (4-14 weeks after the delivery). Brachial artery blood pressure was assessed in the supine position and central artery stiffness was assessed via carotid-femoral (aortic) pulse wave velocity (cfPWV) and carotid β-stiffness index. Endothelial function was determined via brachial artery flow-mediated dilation (FMD). Brachial artery systolic, diastolic, and mean blood pressures were not different between AMA and younger women across pregnancy or postpartum (all
P
>0.05). The AMA group had higher cfPWV (
P
<0.01) and carotid β-stiffness index (
P
<0.01) across pregnancy and postpartum compared to the younger group. cfPWV decreased among younger women at the second and third trimesters compared with the first trimester (
P
<0.01), while cfPWV among women of AMA did not change (
P
=0.07). There were no differences in FMD between AMA and younger women across pregnancy or postpartum (
P
=0.96). These results demonstrate that healthy women of AMA have increased central artery stiffness, but no difference in endothelial function, compared to younger pregnant women across pregnancy, and that the normal decrease in aortic stiffness is blunted in pregnant women of AMA compared to younger women. The sustained higher central artery stiffness throughout pregnancy among women of AMA may contribute to increased risk of pregnancy complications and future CVD risk in these women.
Abstract MP29: Preeclampsia Dysregulates The MicroRNA Profile Of Small Extracellular Vesicles From Endothelial Colony Forming Cells
Authors: Hall Eva , Alderfer Laura , Haneline Laura , Hanjaya-Putra Donny
Published: October 2024

Umbilical cord blood contains an enriched population of endothelial colony forming cells (ECFCs), which are vital for
de novo
vasculogenesis and vessel homeostasis. Previously, our lab has shown that preeclampsia (PE), a hypertensive disorder of pregnancy seen after 20 weeks of gestation, causes perturbations in how the ECFCs function, including decreased vasculogenic potential, and could cause increased risks to the infant later in life. Developing methods to monitor and restore the changes in these cells could significantly improve fetal outcomes. One such method is monitoring small extracellular vesicles (sEVs), which contain a cargo of RNA, DNA, and proteins that can influence other cell’s function through paracrine signaling. By quantifying microRNA (miRNA) expression in the PREC sEVs, we aim to identify potential biomarkers and determine their ability to restore PREC functionality.

ECFCs from healthy (ECFCs) and preeclamptic (PRECs) pregnancies were isolated from cord blood. Three low passage (P4-5) and three high passage (P7-8) cell lines were used for each condition. The supernatant from each cell type was collected, filtered, and ultracentrifuged to isolate the sEVs. The miRNA isolated from the sEVs was quantified using the Nanostring nCounter. Results were assessed using nSolver for data normalization, R for differential expression, and MetaCore for pathway analysis. High and low passage ECFC sEVs were added to the media of the PRECs (1x10
8
sEVs/mL). After 24 hours of treatment, a tube formation assay was run.

There is significant dysregulation of miRNA in the PRECs compared to the ECFCs. Most of the miRNA were associated with proliferation, gene transcription, migration, and angiogenesis. In addition, there are some PE associated functions affected including endometrial remodeling, decidualization, and embryonic development. After treating the PRECs with ECFC exosomes of high and low passages, the PRECs had a more distinct network with clear loops and more branching compared to the untreated control.

PE causes a distinct miRNA profile in PRECs. This data suggests that the dysregulated profile could be used as biomarkers to assess the progression of PE as some miRNA was identified in high or low passage only as well as provide a method for earlier diagnosis. In addition, treatment with healthy sEVs improving PREC tube forming ability indicates their potential as a therapeutic for enhancing vascularization post-PE and improving perinatal outcomes.
Abstract P104: Kidney arteriolar responses to liver-targeted small interference RNA (siRNA) targeting angiotensinogen in diabetic rats: comparison with other renin-angiotensin system blockers
Authors: Cruz-Lopez Edwyn , Martini Alexandre , Foster Don , Zlatev Ivan , Kasper Anne , Sequeira Maria Luisa , Gomez Ariel , Danser Jan
Published: October 2024

Objective:
Inhibition of the renin-angiotensin system (RAS) with ACE inhibitors (ACEi) or angiotensin receptor blockers (ARB) is associated with concentric thickening of renal arteries and arterioles and parenchymal disease. Here we evaluated to what degree this also occurs during RAS inhibition with siRNA targeting hepatic angiotensinogen (AGT).

Methods:
Male hypertensive heterozygous transgenic rats overexpressing mouse renin (TGR(mRen2)27 rats), made diabetic with streptozotocin, were treated with the ARB valsartan (4 mg/kg/day), the ACEi captopril (6 mg/kg/day), AGT siRNA (30 mg/kg every 2 weeks), AGT siRNA + valsartan, or captopril + valsartan for 3 weeks, starting at 15 weeks after induction of diabetes. After 3 weeks of treatment, kidneys were removed, and immunocytochemistry was performed on Bouin’s fixed kidney sections using antibodies against renin or α-smooth muscle actin. Juxtaglomerular index and wall thickness were assessed using tiling pictures of both renin and α-smooth muscle actin sections from the slides. Tubular degeneration was scored by summing up scores for tubular atrophy, interstitial fibrosis, and tubulointerstitial inflammation. Concentric vascular hypertrophy was assessed in a blinded manner.

Results:
All treatments increased juxtaglomerular index, and the largest increases were observed in dual treatment groups, consistent with the highest degree of RAS blockade in these groups. Tubular scores increased after induction of diabetes, and the highest scores were seen in dual treatment groups, significance versus vehicle being reached in the valsartan + captopril group only (P<0.05). Afferent arteriole wall thickness increased in all treatment groups, and the greatest increases were observed during dual treatment. Finally, concentric vascular hypertrophy was observed in 1 of 7 (14%) diabetic Ren2 rats; this percentage increased during RAS blocker treatment of these rats, numerically reaching the highest values during dual treatment.

Conclusions:
Our data suggest that, in the hypertensive diabetic rat model, high levels of RAS blockade, irrespective of the type of blockade, may result in an increase in afferent arteriole thickness and concentric vascular hypertrophy. AGT siRNA in combination with RAS inhibitors should be further explored in clinical studies.
Abstract P114: Reducing Racial Disparities in Hypertension Control using Multicomponent, Equity-Centered Approach
Authors: Kioko Susan , Council Christina , Tomori Cecilia
Published: October 2024

Background:
Black Americans have the highest prevalence of hypertension among all racial or ethnic groups in the United States and are five times more likely to die from hypertension compared to non-Hispanic whites. Perceived discrimination in healthcare, clinician and institutional bias, and socioeconomic and environmental inequities contribute to uncontrolled hypertension in this population. Multilevel, multicomponent interventions have effectively improved blood pressure control among Black Americans but remain inadequately implemented in the clinical setting. An integrated nursing/public health quality improvement study was designed to address this gap between evidence and integration into clinical practice.

Methods:
Using a one group pre/posttest design, we examined the effect of a 12-week intervention on blood pressure among Black Americans with uncontrolled hypertension aged 18 and older in the primary care setting. Intervention components included remote blood pressure monitoring, weekly phone coaching with culturally congruent care, medication intensification, and a standardized hypertension protocol.

Results:
The average age of the participants (n=35) was 64 years, and two thirds (n=23) were female (66%). The mean difference in both systolic and diastolic blood pressure decreased significantly (23 mmHg and 11mmHg, t-test –9.736 and –5.502, p-value <.001). At 12 weeks, 87% of participants had achieved blood pressure control. The intervention also significantly improved medication adherence and hypertension knowledge (p-value <.001).

Conclusion:
A multicomponent, culturally congruent quality improvement intervention significantly improved blood pressure among Black Americans.

Implications:
Scaled up implementation of multicomponent, equity-centered, culturally congruent approaches are needed to reduce racial disparities in hypertension control.
Abstract P129: Assessing the impact of serum lead levels on kidney function Among hypertensive population: NHANES 2017-2020
Authors: KOOKANOK Chutawat , Rodsom Kamonluk , Poochanasri Methavee , Noree Wanprapit , Chuenchaem Urairat , Lertsakulbunlue Sethapong , Phoonakh Thutpharritchn , Bhuriveth Varathpavee , Deepan Natee , Tantisattamo Ekamol
Published: October 2024

Purpose:
Hypertension and chronic kidney disease is known adverse effects of lead poisoning. However, there is limited evidence on the magnitude of the relationship between blood lead levels and kidney function, especially on a national scale. This study investigates the association of serum lead levels (Pb-S) with estimated glomerular filtration rate (eGFR).

Method:
A national study of 6,789 adults, using NHANES 2017-2020 data, analyzed the correlation between Pb-S and eGFR. Participants were categorized into non-hypertension and hypertension groups based on self-reported for doctor diagnosis, with three linear regression models employed.

Results:
In our population, 35.6% have been diagnosed with hypertension, with 36.1% in males and 35.2% in females. The average SBP and DBP were 130.7 ± 17.8 mmHg and 77.6 ± 12.7 mmHg, respectively. The average Pb-S level was 1.04 ± 0.68 µg/dL, with 1.16 ± 0.72 µg/dL for males and 0.94 ± 0.63 µg/dL for females (mean difference 0.22 ± 0.02, P<0.001). Individuals with hypertension had higher mean Pb-S levels compared to those without hypertension (1.15 ± 0.70 vs. 0.98 ± 0.66 µg/dL; mean difference 0.17 ± 0.02, P<0.001). In the final adjusted model, eGFR declined by -1.28 (95% CI: -2.16 to -0.39) in the total group, by -0.35 (95% CI: -1.50 to 0.80) in the non-hypertension group, and by -2.50 (95% CI: -3.90 to -1.11) in the hypertension group, respectively (Fig 1).

Conclusion:
The Pb-S is inversely associated with kidney function in adult hypertensive population in the United States Testing for Pb-S may be considered to especially in hypertensive patients with declined kidney function who are at risk for lead exposure or toxicity.
Abstract P134: Effects of Antihypertensive Medications on All-cause Dementia: Evidence from Target Trial Emulation of 3 Million US Veterans
Authors: Xu Yizhe , Derington Catherine , Greene Tom , Scharfstein Daniel , Andrews Ryan , Berchie Ransmond , Zhang Chong , Supiano Mark , Williamson Jeff , Pajewski Nicholas , Pruzin Jeremy , Shulman Rachel , Cohen Jordana , Bress Adam
Published: October 2024

Introduction:
Hypertension is a modifiable risk factor for all-cause dementia. Mechanistic and observational evidence suggest angiotensin receptor blockers (ARBs) and angiotensin converting enzyme inhibitors (ACEIs) may differentially affect dementia risk.

Objective and Methods:
We used longitudinal electronic health records of over 3 million US Veterans to conduct a target trial emulation with a new-user, active comparator design. We compared the intention-to-treat effect of initiating ARBs vs ACEIs (1/1/2000-12/31/2022) on dementia risk. We controlled for >60 baseline covariates using inverse probability (IP) of treatment and overlap weighting. Dementia was ascertained using diagnosis codes and medications. We nonparametrically estimated the cause-specific cumulative incidence for each treatment group under the competing risk of death then computed treatment effects as weighted risk ratios with bootstrapped 95% confidence intervals. We also evaluated all-cause death and a composite outcome of dementia or death (dementia/Death) using Cox regression.

Results:
Among the 3,190,356 included Veterans (mean age 63, 5% female, 64% White, and 15% Black), 13% initiated ARBs and 87% initiated ACEIs. Overall, 8% developed dementia and 35% died over a median follow-up of 8 years. The risk of dementia was lower among ARB vs ACEI initiators (10-year risk ratio: 0.95 (0.94, 0.96)). The risk of all-cause death and dementia/Death were also lower among ARB vs ACEI initiators with overlap weighting.

Conclusions:
Among US Veterans with hypertension, ARB vs ACEI initiation was associated with a moderately lower risk of dementia. Future work assessing sustained treatment with ARB vs ACEI is needed to inform their use to reduce dementia risk.
Abstract P137: Real-World Impact of Semaglutide on Cardiometabolic Risk Factors in Patients without Diabetes: A Multi-Center Analysis of Electronic Health Records
Authors: Kim Chungsoo , Liu Yuntian , Jastreboff Ania , Khera Rohan , Krumholz Harlan , Brush John , Lu Yuan
Published: October 2024

Introduction:
In randomized controlled trials, semaglutide reduces cardiovascular risks in individuals with obesity/overweight without diabetes. However, its real-world impact on cardiometabolic risk factors remains unclear in this group.

Methods:
We conducted a multi-center analysis of electronic health records data from Yale New Haven Health (01/2018-12/2022) and Sentara Health (01/2018-06/2023). The study population included adults without diabetes mellitus who were prescribed semaglutide and had regular follow-ups over 24 months. The index date was the date of the first prescription of semaglutide. The percent (%) change in weight from baseline and blood pressure (BP) (mmHg) were fit in separate linear regression models. A random-effects meta-analysis was used to synthesize the results from different sites.

Results:
A total of 523 patients without diabetes prescribed semaglutide at Yale and Sentara were included in the analyses. The study population had a mean (SD) age of 56.6 (12.6) years, 69.6% were female, and the mean (SD) BMI was 37.9 (8.4) kg/m
2
. We observed a continuous decrease in body weight over 24 months (Figure 1). At 18-23 months, body weight among these patients was significantly reduced by 4.8 % (2.2, 7.4%). Systolic BP was significantly reduced by 2.03 mmHg (0.4, 3.7 mmHg) at 18-23 months, while there was no significant change in diastolic BP at the end of the study period.

Conclusions:
This multi-center analysis provided preliminary results of the impact of semaglutide on body weight and BP in real-world settings in individuals without diabetes. These findings highlight the importance of post-market surveillance of novel anti-obesity medications.
Abstract P140: Social Determinants of Health and Biologic Measures Differ by Hypertension Treatment Status Between Participants in Two Similar Clinical Trials
Authors: Totwani Mansi , Cao Jingyi , Col Hannah , Turkson-Ocran Ruth-Alma , Zhang Mingyu , Aidoo Emily , Budu Marian , Nartey Sarah , Juraschek Stephen
Published: October 2024

Background:
A disproportionate number of Black adults do not receive hypertension (HTN) treatment. Identifying the social determinants of health (SDoH) and biologic measures related to HTN treatment among Black adults may inform clinical strategies that promote HTN control.

Objective:
To identify SDoH and physical measures associated with HTN treatment among participants of two community-based trials. We hypothesized that SDoH and biologic measures would be associated with HTN treatment.

Methods:
GoFresh (NCT05121337) and GoFreshRx (NCT05393232) are two randomized controlled trials with a shared recruitment drive, investigating the effectiveness of home-delivered DASH-patterned groceries on blood pressure among Black adults with untreated and treated HTN, respectively. HTN treatment was self-reported during prescreening. We examined the association of SDoH and biologic measures with HTN treatment, using logistic regression adjusted for age and sex.

Results:
All participants were Black with mean age 45.8 (SD 16.1) yr and 36.9% on stable HTN treatment. Age, having a primary care physician, higher depressive symptoms, higher body mass index, and higher triglycerides were associated with hypertension treatment, while home ownership and higher high density lipoprotein cholesterol were associated with lower odds of HTN treatment (
Table
). Other factors did not significantly differ among participants in the two trials (notably, household income, insurance status, education, and food insecurity).

Conclusion:
In this community sample of Black adults, multiple SDoH and biologic factors were associated with HTN treatment. Future research should examine whether interventions addressing these factors can improve treatment rates.
Abstract P147: Inappropriate Activation of the Leptin-Aldosterone-Endothelial Mineralocorticoid Receptor Axis Promotes Salt Sensitivity of Blood Pressure in Young Female Mice
Authors: Menik Ishara M.G. , Jordan Coleton , Barris Candee , Kennard Simone , JAISSER Frederic , Belin De Chantemele Eric
Published: October 2024

While compelling clinical evidence indicates that women are more salt-sensitive than men, the mechanisms of the onset of women’s salt-sensitive blood pressure (SSBP) remain largely elusive. Herein, we employed salt-sensitive (SS)-Balb/C and salt-resistant (SR)-C57Bl/6 mice to investigate the etiopathology of SSBP in females. We hypothesized that a high-salt diet alters the leptin-aldosterone-endothelial mineralocorticoid receptor axis (ECMR), leading to SSBP and vascular dysfunction in young SS-female mice. Eleven-week-old female mice were fed a normal (0.4%, NSD) or a high salt diet (4%, HSD) for 7-days. We implanted radiotelemeters for BP monitoring at baseline, HSD, and in response to the leptin receptor (LepR) blockade combined with HSD. Following euthanasia, mesenteric arteries are isolated to measure vascular function via wire myography. HSD elevated mean arterial pressure in Balb/C (NSD: 98.4±2.3 vs. HSD: 105.1±0.9 mmHg) but not in C57 mice (NSD: 99.3±0.9 vs. HSD: 101.3±0.5 mmHg). However, SS-Balb/C mice showed superior natriuretic function in response to salt loading experiments (NSD: 13.3% vs. HSD: 42.3%) as opposed to C57 mice (NSD: 25.8% vs. HSD: 35.1%) (N=3). HSD feeding notably blunted endothelial relaxation to acetylcholine in Balb/c (NSD: 96.5% vs. HSD: 75.4%, N=7), an effect not seen in C57. SS-Balb/C mice failed to suppress aldosterone and adrenal aldosterone synthase (CYP11B2) levels (protein and transcript) compared to C57 mice. This concomitated a 1.8-fold increase in adrenal steroidogenic acute regulatory (StAR) mRNA in SS-Balb/C mice. HSD raised CYP11B2 protein levels in the visceral adipose tissue (VAT) of Balb/C mice. Leptin regulating CYP11B2 expression; we measured fat mass, leptin, and LepR expression. HSD enhanced fat accumulation (C57: +0.7% vs. Balb/c: +26.5%, N=12), leptin levels, and LepR transcript in the adrenal and VAT only in Balb/C mice. LepR blockade reduced BP in Balb/C mice fed a HSD (HSD: 105.1±0.9 vs. HSD+Allo-aca: 100.3±1.9 mmHg). HSD elevated ECMR expression only in Balb/C mice (N=6). To test the potential role of aldosterone-mediated ECMR activation in SSBP, we employed mice with selective overexpression of MR in endothelial cells (ECMR-OE). ECMR-OE young female mice exhibited impaired endothelial function (N=7), reproducing the effects of HSD. In conclusion, SSBP involves an over-activation of the leptin-aldosterone axis in both adrenal and adipose tissue, along with an escalated ECMR expression in females.
Abstract P157: Acute GPER1 Activation Reduces Blood Pressure during the Inactive Period in Aged Female Mice
Authors: Kulthinee Supaporn , Nasci Victoria , Singh Ravneet , Natale Christopher A. , Gohar Eman
Published: October 2024

Non-dipping of blood pressure (BP) during the nighttime is an independent risk factor for hypertension. Importantly, BP dipping is diminished in postmenopausal women, suggesting that the female sex hormones may contribute to the circadian rhythm of BP. Estradiol, activates the G protein-coupled estrogen receptor 1 (GPER1), which elicits protective actions within the cardiovascular system. However, little is known about the GPER1 effect on circadian BP regulation in aged females. Taken together, we hypothesized that systemic GPER1 activation lowers BP and regulates circadian rhythm of BP in aged females. To test the hypothesis, 23-24 months-old C57BL/6J female mice (n=6) were implanted with radio-telemeters for BP recording. After 21 days of postsurgical recovery, BP was recorded. Mice were then given vehicle intraperitoneally daily for 3 consecutive days, followed by the selective GPER1 agonist (LNS8801, 400 µg/kg/day) for an additional 3 days. Data were collected over 24-hour periods according to the 12-hour active period and the 12-hour inactive period. GPER1 activation lowered 24-hour mean arterial pressure (MAP) compared to vehicle control values (113±3 vs. 117±3 mmHg; p=0.01). Similar to MAP, 24-hour systolic blood pressure (SBP) and diastolic blood pressure (DBP) were lower in LNS8801-treated mice compared to corresponding vehicle-treated mice. However, there was not a significant difference in 24-hour heart rate (HR). Interestingly, MAP during the inactive period was lower in LNS8801-treated mice compared to corresponding vehicle-treated mice (104±2 vs. 110±3, respectively, p=0.02). Whereas, GPER1 activation did not elicit significant changes in MAP during the active period. Similarly, LNS8801 reduced DBP during the inactive period (88±4 vs. 96±4 mmHg; p=0.04). We extended the study in aged female mice (14–16 months) with genetic deletion of GPER1 (GPER1 KO; n=6) and wildtype littermates (WT; n=5). Genetic deletion of GPER1 increased 24-hour MAP, SBP, and DBP, whereas HR was not significantly different between genotypes. Noteworthy, GPER1 KO increased MAP during the active period (126±2 vs. 114±1 mmHg; p=0.009) and during the inactive period, compared to WT (110±3 vs. 101±1 mmHg; p=0.01). The results indicate that GPER1 activity lowers BP. Interestingly, LNS8801 acutely improves BP dipping during the inactive period. Overall, GPER1 activation elicits BP-lowering effects in aged female mice, possibly by regulating the circadian BP rhythm.
Abstract P161: A Single-Short Partial Reprogramming of the Endothelial Cells Decreases Blood Pressure Via Attenuation of Endothelial-to-Mesenchymal Transition in Hypertensive Mice
Authors: Pernomian Laena , Waigi Emily , Nguyen Vi , Mohammed Ahmed , JanuarioDa Costa Tiago , Fontes Milene , Kubinack Jason , Aitken Andrew , Biancardi Vinicia , Sinclair David , McCarthy Cam , Tan Wenbin , Wenceslau Camilla
Published: October 2024

Small artery remodeling and endothelial dysfunction are hallmarks of hypertension. Growing evidence supports a likely causal association between cardiovascular diseases and the presence of endothelial-to-mesenchymal transition (EndMT). EC reprogramming represents an innovative strategy in regenerative medicine to prevent deleterious effects induced by cardiovascular diseases. Using reprogramming of ECs, via overexpression of Oct-3/4, Sox-2, and Klf-4 (OSK) transcription factors, we aimed to bring ECs back to a youthful phenotype in hypertensive mice. Mouse ECs were infected with lentiviral vectors (LV) containing the specific EC marker cadherin 5 (Cdh5) and the fluorescent reporter enhanced green fluorescence protein (EGFP) with empty vector (LVCO) or with OSK (LV-OSK). Confocal microscopy and western blotting analysis were used to confirm the OSK overexpression. Human aortic ECs (HAoECs) from male and female normotensive and hypertensive patients were analyzed after OSK or control treatments for their endothelial nitric oxide synthase (eNOS) levels, nitric oxide (NO), and genetic profile. Male and female normotensive (BPN/3J) and hypertensive (BPH/2J) mice were treated with an intravenous (i.v.) injection of LVCO or LV-OSK and evaluated 10 days post-infection. The blood pressure, vascular reactivity of small arteries,
in vivo
EGFP signal and EndMT inhibition were analyzed. Data were analyzed using One-way or Two-way ANOVA, with Tukey post-hoc (
p
<0.05). OSK overexpression induced partial EC reprogramming
in vitro
. OSK treatment of male but not female hypertensive BPH/2J mice normalized blood pressure (BPH/2J LVCO: 105±2mmHg, n=6
versus
BPH/2J LV-OSK: 90±2mmHg, n=5) and resistance arteries hypercontractility (BPH/2J LV-CO: 10.50±0.82mN
versus
BPH/2J LV-OSK: 7.12±0.6mN, n=5), via the attenuation of EndMT (BPH/2J LVCO: 0.041±0.01AU, n=3
versus
BPH/2J LV-OSK: 0.007±0.004 AU, n=3) and elastin breaks. EGFP signal was detected
in vivo
in the prefrontal cortex of BPN/3J and BPH/2J-treated mice, but OSK induced angiogenesis in male BPN/3J mice. OSK-treated human ECs from hypertensive patients showed high eNOS activation and NO production, with low ROS. Single-cell RNA analysis showed that OSK alleviated EC senescence and EndMT, restoring their phenotypes in human ECs from hypertensive patients. Overall, these data indicate that OSK treatment and EC reprogramming can decrease blood pressure and reverse hypertension-induced vascular damage.
Abstract P168: The Unholy Link: The Herbicide Glyphosate Contributes to Hypertension, Gut Microbiota Dysbiosis, and Sympathetic Overdrive
Authors: Manandhar Ishan , Tummala Ramakumar , Aryal Sachin , Mell Blair , Mei Xue , Alviter Plata Adriana , Kandalgaonkar Mrunmayee , Vijay-Kumar Matam , Zubcevic Jasenka , Joe Bina
Published: October 2024

Introduction:
Glyphosate, marketed as Roundup®, is a widely used potent herbicide in the US. Glyphosate inhibits 5-enolpyruvylshikimate-3-phosphate synthase of the shikimate pathway, a non-mammalian signaling pathway present in plants and microbes. Therefore, glyphosate has been deemed safe for humans. However, humans are holobionts with symbiotic gut microbiota susceptible to gut dysbiosis when exposed to glyphosate. Because gut microbiota is an important contributor to hypertension (HTN), we hypothesized that exposure to glyphosate leads to gut dysbiosis and HTN.

Methods:
Dahl salt-sensitive (S) rats were administered either vehicle or glyphosate (175 mg/kg/day) in drinking water for three weeks ad libitum. In one group of rats (N=4/group), sympathetic nerve activity was assessed using in situ whole nerve recordings and by measuring circulating norepinephrine (NE) levels by ELISA. In separate rats (N=6–8/group), blood pressure (BP) was measured once a week for three weeks by radiotelemetry, and circulating NE was determined by ELISA. At the endpoint, fecal microbiome analyses were performed using the Illumina and Oxford Nanopore platforms.

Results:
Exposure to glyphosate for just one week was sufficient to significantly increase systolic (173 mmHg vs 160 mmHg, p<0.0001) and mean arterial pressure (MAP) (148 mmHg vs 141 mmHg, p<0.0002), but not diastolic BP of S rats. Through week three, BP continued to rise in glyphosate-treated rats with greater differences in the systolic (195 mmHg vs 176 mmHg, p<0.0001), diastolic (142 mmHg vs 135 mmHg, p<0.0001), and MAP (168 mmHg vs 155 mmHg, p<0.0001). This was accompanied by increased sympathetic nerve activity and serum NE as early as one week of exposure to glyphosate (5.85 ng/mL vs 4.77 ng/mL, p<0.001), which continued at week three of glyphosate exposure (13.31 ng/mL vs 6.16 ng/mL, p<0.001), indicative of adrenergic overdrive. 16S data showed that glyphosate altered the composition of commensal gut microbiota, reducing bacterial α-diversity (Shannon entropy; p<0.05) and β-diversity (Bray-Curtis; p<0.02). Whole metagenomic analysis revealed a higher abundance of several bacterial species, including
Candidatus
spp.,
Erysipelaclostridium ramosum
, and
Clostridium sporogenes
in the glyphosate-treated rats.

Conclusions:
Glyphosate exposure elevated BP, increased sympathetic nerve activity, and altered gut microbiota composition. This is the first proof-of-concept study to demonstrate that glyphosate contributes to HTN.
Abstract P199: Renal kallikrein-1 is not essential in adaptation to an overnight potassium load
Authors: Curry Josh , Su Xiao-tong , Maeoka Yujiro , Yang Chao-Ling , Delpire Eric , Welling Paul , Ellison David
Published: October 2024

Background:
Kallikrein-1 is a serine protease expressed in multiple tissues including the kidney, where it is secreted into the urine. Low urinary kallikrein levels are associated with essential hypertension, whereas high levels are associated with primary hyperaldosteronism in humans. Global kallikrein-1 deletion in mice has been shown to lead to hyperkalemia in response to an acute potassium load as well as defective cleavage of gamma-ENaC, suggesting a direct role in distal K
+
handling. However, it remains unclear whether effects seen with global kallikrein-1 loss are secondary to loss of extrarenal or renal kallikrein, which is primarily expressed in the connecting tubule.

Methods:
To test the hypothesis that renal kallikrein-1 is necessary for increased K
+
secretion in response to acute dietary K
+
load, we generated mice with conditional knockout of kallikrein-1 in the distal tubule (Klk1 flox - Calbindin-Cre, KS-Klk1 KO). Mice were treated with a K
+
deficient diet (0% K
+
, LK) for 9.5 days and then placed in metabolic cages for 12hr overnight collection of urine on control (LK) or high K
+
(5%, OHK) diets. Metabolic parameters in plasma were measured using iSTAT and kidneys were harvested for downstream western blotting.

Results:
Deletion of kallikrein-1 in KS-Klk1 kidney was confirmed by western blotting and urine kallikrein activity assay. On LK diet, both WT and KS-Klk1 KO mice developed marked hypokalemia (WT 2.83+/-0.23 vs KO 2.88+/-0.15 meq/dL). Following OHK challenge, hyperkalemia developed to similar levels in both groups (WT 7.13+/-0.56 vs KO 7.74+/-0.35). However, KS-Klk1 KO mice with HK challenge exhibited a more pronounced drop in serum [Na
+
] compared with WT (WT 142.6+/-1.4 vs KO 136.6+/-1.3, p=0.022) and correspondingly lower serum [Cl
-
] (WT 119.0+/-0.62 vs KO 115.9+/-0.96). Gamma-ENaC quantitation by western blot revealed similar ratios of cleaved: uncleaved species between genotypes. No significant changes between genotypes were detected in urine volume or urine Na+/K+ ratios.

Conclusions:
KS-Klk1 KO mice do not display defective K+ handling or ENaC processing in response to an acute 12 hr overnight high K
+
diet. However, they do display relative hyponatremia compared with WT. These data may suggest compensatory mechanisms for potassium transport or a direct a role for renal kallikrein-1 in regulation of renal water transport.
Abstract P208: Chromophobe Renal Cell Carcinoma Presenting as Hypertension in a Young Adult: A Case Report
Authors: Al Kayed Hadeel , Alqatawneh Maryam , Maaita Mahmoud , Alsuradi Awni , Odaibat Husam
Published: October 2024

Introduction:
Renal cell carcinoma (RCC) is a recognized but rare cause of secondary hypertension. Hypertension in RCC can arise through several mechanisms, including direct renin secretion by the tumor (renin-secreting RCC), the tumor creating a mass effect on renal blood supply, decreasing it and activating the RAAS, or the presence of adrenal tissue within the tumor. Given these mechanisms, it is essential to consider renal tumors in the differential diagnosis of secondary hypertension. This case reports uncontrolled hypertension as the presenting complaint in a young female with a chromophobe RCC.

Case Presentation:
A 32-year-old female presented with intermittent headache, fatigue, and uncontrolled hypertension despite adherence to standard antihypertensive treatment. Laboratory tests revealed serum aldosterone at 37.9 ng/dL and markedly elevated plasma renin activity at 11.7 ng/mL/hr, suggesting hyperreninemic aldosteronism as the cause of her hypertension.

A CT scan revealed a large, mildly enhancing mass in the upper pole of the left kidney, measuring 93 x 92 x 96 mm (Figure 1).

Nephrectomy was discussed with the patient as part of her treatment plan and as a potential means of treating her hypertension. The patient consented, and the surgery was performed. Microscopic examination confirmed a chromophobe RCC extending into the renal sinus.

Conclusion:
This case underscores the importance of considering RCC in the differential diagnosis of secondary hypertension, even in young adults. Early recognition and surgical intervention, such as nephrectomy, are crucial, as they may alleviate hypertension and potentially serve as an early indicator for tumor detection before further progression.
Abstract P212: Microinjection of the novel angiotensin, alamandine-(1-5) into insular cortex, increase blood pressure
Authors: MARINS Fernanda , Godoy Ana , Monteiro Adelson , Peliky Fontes Marco Antonio , Santos Robson
Published: October 2024

It is well known that the renin-angiotensin system plays a critical role in cardiovascular control and hydro-electrolyte homeostasis. At least in some circumstances Alamandine (Ala) and Angiotensin-(1-7) can have selective actions such as reported in the insular córtex (IC). Hydrolysis of Angiotensin-(1-7) by angiotensin converting enzyme (ACE) can form the heptapeptide Angiotensin-(1-5) and recently our group demonstrated that hydrolysis of Ala by ACE can form Ala-(1-5). In this study we aimed to evaluate the cardiovascular effects produced by microinjection of Ala-(1-5) and Angiotensin-(1-5) into the rostral region of the posterior IC.

Urethane (1.4g/kg) anesthetized rats were instrumented for measurement of mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA). Unilateral microinjection of vehicle (0,9% NaCl, 100nL, n=4), Ala (40pmol/100nl, n=7), Ala-(1-5) (400pmol/100nl, n=7) or Angiotensin-(1-5) (400pmol/100nl, n=5) were made into IC (+1.5mm rostral to the bregma).

At the baseline, there was no difference between the groups (Vehicle: 85±2 mmHg and 388±5bpm, Ala: 83±9mmHg and 389±10bpm, Ala-(1–5): 91±6mmHg and 386±7bpm or Ang-(1-5): 96±9mmHg and 375±6bpm). Vehicle microinjection was performed as a control for nonspecific effects (ΔMAP:2±1mmHg, ΔHR:4±2bpm, ΔRSNA:3±1%). Ala microinjection into IC, confirmed our previous data showing a long-lasting (18±3min) increase in MAP (Δ=14±2mmHg), and this effect was associated with a significant increase in HR (Δ=32±4bpm) and in RSNA (Δ=36±6%). These responses were elicited immediately after Ala microinjection.

When compared with vehicle and, very different from what was observed with Ala, microinjection of Ala-(1–5) evoked a significant increase in blood pressure without altering RSNA or HR (ΔMAP:22±2mmHg, ΔHR:-1±3bpm, ΔRSNA:1±3%). Differently from Ala evoked responses, the effects of Ala-(1–5) had a shorter duration (5.88±1.9min) without delay to beginning the effects. On other hand, microinjection of Angiotensin-(1-5) did not elicited autonomic and cardiovascular effects (ΔMAP:-1±3mmHg, ΔHR:-2±2bpm, ΔRSNA:2±3%).

In conclusion, these data showed that the IC is a brain site that has unique effects of Ala (increase in MAP, HR and RSNA) and Ala-(1-5) (increase in MAP only) contrasting with the essentially absent effects of Angiotensin-(1-7) and Angiotensin-(1-5). These findings will contribute to extend our understanding of the brain renin-angiotensin system.