bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P217: The Role Of Angiotensin-(1-7) In Regulating Vascular Endothelial Function In Postmenopausal Women
Authors: Del Vecchio Angelica R , Schwab Allyson I , Edwards David G , Fancher Ibra , Stanhewicz Anna E , Wenner Megan M
Published: October 2023

Postmenopausal women (PMW) have reduced endothelial function, however, the mechanisms contributing to this decline remain unclear. Angiotensin-(1-7) [Ang-(1-7)] is a vasoactive peptide of the vasodilatory arm of the Renin-Angiotensin system and increasing bioavailable Ang-(1-7) enhances endothelial function in young women (YW) with pre-clinical cardiovascular disease. Circulating Ang-(1-7) decreases with aging and may be impacted by menopause. However, whether increasing bioavailable Ang-(1-7) improves endothelial function in PMW is unknown. The purpose of this study was to test the hypothesis that increasing bioavailable Ang-(1-7) improves endothelial function in PMW. We assessed skin blood flow responses to local heating in 8 healthy YW (27±9 yrs) and 5 healthy PMW (56±4 yrs). Cutaneous vasodilation was measured using laser-Doppler flowmetry directly over microdialysis perfusions of lactated Ringer’s (control) in YW and PMW, and in PMW only, 100 μM Ang-(1-7). Following 45 minutes of perfusion of lactated Ringer’s and Ang-(1-7), skin was heated to 42°C (0.1°C·sec
-1
) until laser-Doppler flux reached a stable plateau, indicative of endothelium-dependent dilation. Following the plateau, 28mM sodium nitroprusside was perfused while skin was heated to 43°C to achieve maximal vasodilation. Cutaneous vascular conductance (CVC) was calculated as laser-Doppler flux/MAP, and normalized to maximal dilation (%CVC
max
). Women were normotensive (MAP: YW 86±7 mmHg; PMW 85±9 mmHg) and not obese (BMI: YW 23±3 kg/m
2
; PMW 23±4 kg/m
2
). YW had greater dilation during local heating (control: YW 94.54±5.4 vs. PMW 82.59±10.72 %CVC
max
; P=0.021). Contrary to our hypothesis, Ang-(1-7) did not enhance heating-induced vasodilation in PMW (80.10±9.43 %CVC
max
; P=0.69). These preliminary results suggest that increasing bioavailable Ang-(1-7) may not improve endothelial function in PMW. Additional studies are needed to understand if these findings are due to estrogen deficiency in PMW.
Abstract P227: Resistant Hypertension In Young Patient- A Case Of Conn’S Syndrome
Authors: Marrium Areeba , Viswanathan Swati , Soundarajan Ramesh
Published: October 2023

Abstract:
Resistant hypertension (HTN) is defined as elevated blood pressure (BP) while being on three different antihypertensive medications at maximum recommended doses which include diuretics or BP that requires four different antihypertensives. One of the secondary causes of resistant HTN is Conn's Syndrome (CS). CS is mainly due to excessive secretions of aldosterone (aldo), Aldo is a mineralocorticoid hormone that maintains sodium and potassium homeostasis. Excessive secretion can result in hypernatremia and hypokalemia. This is a case of a young patient who presented with resistant hypertension and low potassium.

Case:
A 47-year-old African American with a known history of HTN presented with a seizure-like episode due to elevated BP and low potassium (K) of 2.6 with a creatinine of 2.2 (baseline creatinine 1.2). He was non-compliant with BP medication hydrochlorothiazide. During hospitalization, BP remained elevated with low K even with K supplementation. BP regimen was broadened to amlodipine, carvedilol, hydralazine, losartan, and spironolactone. Further evaluation showed elevated plasma aldo and low renin with a ratio >30. CT abdomen with contrast confirmed a right adrenal gland adenoma measuring 1.8 cm x 2.0 cm. Ultimately, the patient underwent robot-assisted right adrenalectomy, and adrenal vein sampling (AVS) confirmed CS. The right AVS showed an aldo level >3000 ng/dl and the left adrenal aldo level was 37.6 ng/dl. After successful surgery, BP medicines were cut down to spironolactone. A few months later, BP improved, and all medications were discontinued.

Discussion:
Aldosterone poses proinflammatory, prothrombotic, and profibrotic changes that in the long-term cause end-organ damage. For these reasons, diagnosing hyperaldosteronism early in young patients is crucial to avoid further complications. Adrenalectomy is a treatment of choice in most cases, many patients could also benefit from pharmacotherapy, especially with newer medications that are not anti-androgenic and nonsteroidal like finerenone. Hyperaldosteronism can be simply diagnosed by checking serum morning aldo level and renin level. Therefore, screening for hyperaldosteronism should be done frequently in young patients with resistant HTN.
Abstract P317: Methylene Blue Preserve The Microcirculation And Reduces Death In Rats Inflammation Models
Authors: Dantas Pedro , Mestriner Fabiola L , Couto Ariel , Fagundes Agnes , Michelon Barbosa Jessyca , Evora Paulo Roberto B , Becari Ribeiro Christiane , Ribeiro Mauricio , Flora Vinicius
Published: October 2023

Introduction:
Sepsis is a serious medical condition in response that occurs when the body responds to an infection in an exaggerated way, causing a widespread inflammation that can lead to damage in multiple organs and systems of the body. Sepsis mortality is high, and new and old drugs are being studied to help maintain hemodynamic stability as methylene blue (MB). MB has been used to increase the blood pressure in sepsis showing to be efficient in rebalancing circulatory integrity in physiological patterns. We sought to investigate methylene blue treatment in the sepsis survival rate and mesenteric microcirculation preservation.

Methods:
Male Hannover rats from University of São Paulo (USP)were treated by intravenous bolus with MB (4 mg/kg) or saline. Mild sepsis was induced by CLp with 4 holes, moderate sepsis with 10 holes, and severe sepsis with 20 holes in the cecum using a 16-gauge needle. The rats survival was observed during 9 days after surgery and expressed as the percentage of animals surviving by the log-rank test (X2, chi-square). Intravital microscopy was performed to evaluate the integrity of the mesenteric microcirculation by analyzing the leukocyte rolling and adhesion by lipopolysaccharide(LPS) sepsis model. LPS was administered intraperitoneal and treatment with intravenously MB by femoral vein. Rolling and adhesion were quantified by intravital microscopy in rats that received treatment with MB or saline.

Results:
MB treatment improved survival rate in severe sepsis. Severe sepsis groups with MB had a survival rate of30% (p=0.02). MB treatment did not change survival rate in the mild and moderate sepsis groups. The rats that received LPS showed an improvement of leukocyte adhesion and rolling in mesenteric vessels compared with the saline group. Rats that received only MB had similar results to the saline group. Although, when rats received LPS and were treated with MB (after or before LPS), the leukocytes adhered and rolled in the mesentery diminished significantly (p< 0,001)similarly to the saline group.

Conclusion:
Our data suggest that MB was able to increase survival in the severe sepsis and might be a beneficial drug for the protection of microcirculation.

Funding:
FAPESP, CAPES, FAEPA.
Abstract P323: Going Beyond Spot 30-minute Nocturnal Blood Pressure (bp) Check With The Continuous Nocturnal Bp Monitoring
Authors: Assad Osayd , Amro Tasneem , Sapp Jamie , Cho Yeilim , Zhao Xue-Qiao , Mazimba Sula , Kwon Younghoon
Published: October 2023

Background:
Ambulatory Blood Pressure Monitoring (ABPM) is useful to determine nocturnal BP. However, the major limitation is the spot-check nature. The main objective of the study is to compare the nocturnal blood pressure (BP) results derived from continuous nocturnal (beat-to-beat) finger cuff BP monitoring device (CNBPM) based on pulse decomposition analysis and from conventional arm cuff-based ABPM.

Methods:
We prospectively enrolled 17 subjects from the community. Each subject underwent 1 day of standard 24-hour ABPM. On a second day, the subjects underwent continuous BP monitoring at nighttime only. Systolic BPs (BP hereafter) 12 AM - 6 AM constituted nocturnal BP. We compared the maximum nocturnal BP from ABPM with that from CNBPM. For paired comparison, we matched every 30-minute nocturnal BPs by ABPM, with the corresponding 30 min-averaged nocturnal BPs from CNBPM. Using these data points, we also examined nocturnal dipping by both methods. For continuous BP dipping calculation, we used late night and early AM BP recording (outside 12 AM-6 AM window) derived from continuous BP monitoring. Non-dipping was defined by < 10% BP reduction at nighttime.

Results:
All enrolled subjects recorded both ABPM and CNBPM. Maximum nocturnal BP was lower by ABPM than by CNBPM (
M
71.28,
SD
8.65 vs.
M
96.11,
SD
13.74), p<0.0001). Paired comparison of every 30 min nocturnal BP yielded a lower nocturnal BP by ABPM than CNBPM (113.65 mmHg (18.31) vs. 113.43 (SD 27.32), p = 0.978). The mean absolute dipping was similar between ABPM and CNBPM (13.2% (7) and 9.5 (10.6), p=NS) respectively. Among 8 subjects with normal dipping, 9 subjects were categorized as non-dipping by CNBPM. Among 11 subjects who had normal dipping by ABPM, 6 subjects met non-dipping by ABPM. CNBPM was better tolerated than ABPM according to subjects.

Conclusion:
This study demonstrates that the clusters of BP variability overnight may be missed by a spot-check nocturnal BP measurement by ABPM. There was bias toward the underestimation of BP by ABPM when compared to CNBPM. Further studies should determine a subset of high-risk patients who may benefit from using CNBPM for accurate nocturnal BP monitoring.
Abstract P325: Early Insights From A Self-measured Blood Pressure Program In A Socially And Economically Disadvantaged Primary Care Population
Authors: Cantu Martinez Omar , Hartley Maria , Chacin Suarez Audry , Shah Samir , Rodriguez Jordan , Behme Matthew , Copeland Joshua A
Published: October 2023

Background:
Meta-analyses have shown the success of SMBP in BP control. We aim to describe an SMBP QI program at our primary care clinic and assess its impact on BP. The Einstein CPC is a safety net practice that serves a socially and economically disadvantaged population facing many HTN management barriers.

Methods:
This program utilized a QI approach for BP control and patient-provider connection. Patient demographics, clinical features, and SDOH were assessed at baseline. Patients with uncontrolled HTN (SBP >140 mmHg) were asked to participate. To date, 111 patients enrolled. Patients were given a Bluetooth-enabled BP monitor connected to a mobile health app, HTN education, DASH diet recommendations, and orientation to SMBP protocols. Those reporting social needs or depression were referred to behavioral resources. Health staff continuously telemonitored patient usage, BP, and individualized interventions. We evaluated the difference in BP from baseline BP and estimated the change in time using a linear multilevel model with random intercept and random slope for each patient. We also calculated time in target range defined as time in SBP 100-130 and DBP 70-80 in mmHg.

Results:
Patient characteristics (Table 1). Those with at least 3 d of BP readings - 93% (103/111) were included in the BP analysis (Figure 1); mean follow-up 69±67 d and BP readings 42±52. Over 90 d, SBP, and DBP decreased by 11 (95% CI: 4-17) and 5 (95% CI: 3-8) mmHg, respectively.

Conclusions:
A QI-based SMBP program with robust telemonitoring and individualized interventions may effectively promote short-term adherence to remote BP monitoring and BP control in a socially and economically disadvantaged population.
Abstract P328: A Retro And Prospective Review Of Within Session Clinic Bp Assessment In Hypertenison Clinical Trials
Authors: Heilbraun Jeffrey , Dekie Luc , Connor Kalvin , Rudo Todd
Published: October 2023

There has been an increased interest and discussion around oscillometric blood pressure variability across the use of different BP measurement modalities and technology. Recent publications have referenced the BP variability as Very short term, short term, mid term and long term variability with each variability associated with a specific BP modality. The scientific and medical working groups have referenced the importance of capturing replicate readings during a standard clinic assessment. An area which has not received as much focus is on the assessment of BP variability within a standard clinic assessment with replicate readings. This becomes of specific interest during the conduct of a clinical trial where BP assessment can be a primary efficacy endpoint (hypertension drug development) or safety (Draft FDA Pressor guidance). This abstract will approach this specific area by providing examples and analysis from recent clinical trials which incorporated standardized clinic BP technology and automated sequence of BP readings across the study population. Each of the studies implemented a different sequence of readings and visit averaging function which will also be expanded upon in the presentation as to developing industry and scientific guidelines. Through this abstract and presentation the attendee will be provided present approaches to clinic/office based assessment in clinical trials and decisions around implementation strategies to address observed variability.
Abstract P331: Cumulative Hypertensive Peaks In 24h Blood Pressure And Cardiovascular Risk
Authors: Melgarejo Jesus D , Mena Luis J , Vatcheva Kristina P , Garcia Jose A. , Satizabal Claudia L , Chavez Carlos A. , Pirela Rosa V. , Silva Egle , Calmon Gustavo , Lee Joseph , Terwilliger Joseph , Seshadri Sudha , Maestre Gladys E.
Published: October 2023

Background:
Blood pressure (BP) variability relates to cardiovascular (CV) diseases and one unexplored mechanism may involve hypertensive peaks caused by high BP variability. To test this hypothesis, we studied the association of cumulative hypertensive peaks (CHP) in 24-h systolic BP with CV risk.

Methods:
A total of 1212 participants from the Maracaibo Aging Study (mean age, 66; women, 67.2%) underwent 24-h ambulatory BP monitoring and were followed between 1998 and 2010. BP variability was the 24-h average real variability (ARV). CHP in systolic BP (expressed as %) was the number of systolic BP measures ≥125 mmHg (based on the ACC/AHA threshold) each participant experienced over 24-h divided by the number of recordings. The primary endpoint was a composite of fatal and nonfatal coronary, heart failure, and stroke events, while secondary endpoints were total and CV mortality, and fatal and nonfatal coronary and stroke endpoints. Statistics included adjusted Cox proportional models adjusted.

Results:
During a median follow-up of 8 years, 242 participants developed a composite of any CV endpoint, and 353 died (210 cardiovascular deaths), 129 had coronary and 57 stroke endpoints. An increment of +2 mmHg in 24-h ARV (HR [hazard ratio], 1.18; 95% confidence interval [CI], 1.05-1.33) or +5% in CHP (HR, 1.05; 95% CI, 1.02-1.07) increased CV risk. The inclusion of both indexes in the same Cox proportional models resulted in CHP, but not ARV (
P
=0.075), associated with the primary endpoints (
P
=0.004). For secondary endpoints, the association of ARV attenuated while CHP was similar.

Conclusions:
In this population-based cohort study, CHP in 24-h systolic BP explains the association of high 24-h BP variability and CV risk. Clinical management of high 24-h BP variability is challenging but recognizing that an increased variability results in CHP seems a feasible alternative to address in CV prevention.
Abstract P332: Asynchronous Management Of Hypertension: The Effectiveness Of Remote Patient Monitoring In Mixed Populations
Authors: Smith Wesley , Caven Dean , Ewing Alex , Albano Andrew
Published: October 2023

Background:
This study evaluated the effectiveness of a remote patient monitoring (RPM) program for hypertension (HTN) management in cardiology (CV) and primary care (PC) populations.

Methods:
Patients were provided cellular-enabled blood pressure (BP) cuffs that transmitted data to a practice-integrated portal. Patients who uploaded ≥ 30 BP readings for ≥ 90 days (n=2,761) were included. Clinical staff trained patients to take BP measurements, and patients received calls to discuss medication adherence and care plans. If readings were outside the predetermined range, alerts were sent to practice providers for medical management.

Results:
The study included 2,761 patients, with an average transmission index of 67% for CV (60.7 times per 90 days) and 63% (56.7 times per 90 days) for PC. At enrollment, uncontrolled HTN was prevalent in 65.4% (1345/2057) of CV and 68% (479/704) of PC patients. Post-intervention, there was a significant decrease in uncontrolled HTN to 49.3% (1014/2057) and 60.0% (422/704), respectively (p < 0.001). Both systolic and diastolic HTN improved with reductions of 11.4 mmHg and 8.6 mmHg in SBP and DBP, respectively, in CV patients, and 8.0 mmHg and 4.6 mmHg in PC patients (p < 0.0001). The most significant improvements were observed in patients with stage 2 HTN, achieving SBP and DBP reductions of 20.81 mmHg and 13.9 mmHg in CV patients and 15.9 mmHg and 10.0 mmHg in PC patients (p < 0.0001), respectively. The treatment was also effective in patients with high pulse pressure (PP), with PC patients experiencing an average PP reduction of 6.2 mmHg and a reduction of 5.8 mmHg among CV patients (p < 0.0001).

Conclusion:
RPM can be an effective adjunct therapy to improve HTN management in both primary care and specialty care populations.
Abstract P347: Utility Of Standing Blood Pressure On Blood Pressure Control In Treated Hypertension
Authors: Kositanurit Weerapat , Giacona John M , Wang Jijia , Vongpatanasin Wanpen
Published: October 2023

Many hypertension (HTN) guidelines have recommended routine measurement of standing BP in HTN adults at risk of orthostatic hypotension, especially in older adults. However, the incremental value of adding standing BP to seated BP in predicting HTN control has not been studied. Accordingly, we assessed BP in both seated and standing positions in 319 HTN adults treated with antihypertensive medications. Adequate BP control was defined as 24-Hr ABPM ≤125/75 or daytime ABPM ≤130/80 mmHg. Area under receiver operator characteristic curve (AUROC) was used to determine accuracy of seated and standing BP in assessing BP control. Bayes factor (BF) was used to assess the significant difference between AUROCs. Sensitivity and specificity of standing BP were derived using cutoffs derived from Youden’s Index. Overall mean age was 64±13 years, with 55% women (176 of 319), and 27% Black (86 of 319). Sensitivity and specificity of seated SBP were 75% and 60%, respectively, when HTN control was defined by 24-Hr ABPM. Optimal cutoffs for standing BP were 138/86 and 142/86 mmHg (based on 24-Hr SBP and daytime SBP as gold standard, respectively). Sensitivity and specificity of standing SBP were 54% and 81%, respectively, when using the cutoff derived from 24-Hr ABPM. The AUROCs of standing SBP and DBP were not significantly different compared to seated when HTN control was defined by 24-Hr or daytime ABPM. Similarly, the addition of standing to seated BP was not significantly different when compared to seated BP based on both references (Figure 1: A-B). In conclusion, routine incorporation of standing office BP did not offer additional value in determining adequacy of BP control among treated HTN patients.
Abstract P351: Clinician Continuity And Confirmatory Blood Pressure Measurement Lead To Higher Rates Of Antihypertensive Therapeutic Intensification
Authors: Martin Ben , Sutherland Susan E , Rakotz Michael , Egan Brent M
Published: October 2023

Background:
Evidence supports treatment intensification (TI) as the most important factor impacting BP control. In our modeling of TI from EHR data, 13.2% of variance in TI could be explained. Care process-related factors that influence the rate of antihypertensive (AH) TI are particularly important for informing population-level hypertension control efforts, especially those that are modifiable. This study examines previously unstudied care-process variables: confirmatory (c, repeated) cBP measurement and clinician consistency; and their relationship with TI.

Methods:
Data for defining and modeling AH TI comes from ambulatory primary care clinics at five distinct health care organizations. Mixed-effects logistic regression was used to model the relationship between cBP, clinician consistency, and TI at visits with uncontrolled BP (≥140/≥90 mmHg).

Results:
“Primary clinician” is defined as the clinician most frequently seen by each patient at all primary care visits in the last two years. Visits with cBP measurement had 56.6% greater odds of TI and explained 1.1% of the variance in TI. Visits with a patient’s primary clinician had 55.9% greater odds of TI, accounting for ~1% of variance in TI.

Conclusion:
Repeat or cBP measurements increase the rate of TI as does current and prior visits with the primary clinician, but collectively account for only ~2% of variance in the rate of TI. Increasing continuity of care with the primary provider and frequency of repeated BP values at encounters when BP is uncontrolled could improve the low rate of TI, although other interventions are clearly needed.
Abstract P360: Comparative Analysis Of Hypertension Knowledge: ChatGPT Vs. General Public
Authors: Khidhir Angela
Published: October 2023

Introduction:
Artificial intelligence (AI) has revolutionized the way medical knowledge is obtained and applied in healthcare settings. AI algorithms and models can process and analyze vast amounts of medical data, extract meaningful insights, and assist healthcare professionals in making informed decisions. We conducted a study comparing the hypertension knowledge of ChatGPT, an AI language model, to the general public, assessing the potential of AI in improving awareness.

Methods:
ChatGPT responses were analyzed alongside survey data on blood pressure targets, lifestyle modifications, medication dosages, and monitoring parameters.

Results:
ChatGPT demonstrated proficiency in hypertension management, identifying blood pressure targets and lifestyle recommendations with an accuracy of 85%. The general public had limited awareness, with gaps in target values (45%), lifestyle modifications (<30% dietary, 40% physical activity), medication dosages (25% accurate), and monitoring (35% regular).

Conclusion:
This study reveals knowledge disparities between ChatGPT and the general public. ChatGPT exhibits proficiency, while the general public shows gaps in hypertension knowledge. Effective education initiatives are needed to bridge these gaps and enhance public understanding of hypertension management. AI language models like ChatGPT have the potential to close knowledge divides and improve hypertension awareness.
Abstract P366: Natriuretic Peptides Potentiate Cardiac Hypertrophic Response To Norepinephrine In Rats
Authors: Kato Johji , Jiang Danfeng , Matsuzaki Minami , Ida Takanori , Tsuruda Toshihiro
Published: October 2023

Background:
The natriuretic peptide (NP) family consisting of ANP, BNP, and CNP is assumed to exert protective actions for the heart, alleviating hypertrophy and/or fibrosis of the myocardium. Excessive activation of the sympathetic nervous system is involved in cardiovascular damage including cardiac hypertrophy. In contrast to the previous notion, we show in the present study that both atrial and C-type natriuretic peptides (ANP and CNP) potentiate cardiac hypertrophic response to norepinephrine (NE) in rats.

Methods and Materials:
Nine-week-old male Wistar rats were continuously infused with subcutaneous 30 μg/h NE without or with persistent intravenous administration of either 1.0 μg/h ANP or CNP for 14 days. The NE plus ANP groups were treated orally without or with either 5 mg/day prazosin or 50 mg/day atenolol during this study period. Sample sizes are follows: control, NE, NE plus ANP, n=8 to 9; CNP, NE plus CNP, prazosin, atenolol, n=6 to 7. Blood pressure (BP) was recorded via a catheter placed in the abdominal aorta under an unrestrained condition by a radiotelemetry system. Cardiac hypertrophic response to NE was evaluated by heart weight to body weight (HW/BW) ratio. Left ventricular (LV) tissues were also examined microscopically to measure individual myocyte size and collagen deposition.

Results:
Mean BP levels at the light and dark cycles rose by 20 and 17 mmHg, respectively, following NE infusion for 14 days, with slight increases in HW/BW ratio (+7.6%) and ventricular myocyte size (+20%), compared to control (P>0.05). Infusions of ANP and CNP had no significant effects on mean BP in NE-infused rats, while two natriuretic peptides potentiated cardiac hypertrophic response to NE at day 14 (HW/BW and myocyte size: NE plus ANP, +37% and +64%; NE plus CNP, +47% and +56%, respectively; P<0.01 for all). No differences were noted in collagen volume fraction of LV among all study groups. Cardiac hypertrophy induced by co-administration of NE and ANP was attenuated by treatment with prazosin or atenolol.

Conclusion:
Both ANP and CNP potentiated α1- and β1-adrenergic receptor-mediated cardiac hypertrophic response to continuously infused NE in rats, suggesting a possible pro-hypertrophic action of NPs on the heart.
Abstract P376: Collecting Duct Renin And Its Receptor Contributes To Unilateral Ureteral Obstruction-induced Kidney Injury Via Activation Of The Intrarenal Ras
Authors: Yang Tianxin , Yang Kevin , Wang Fei , Luo Renfei
Published: October 2023

The collecting duct (CD) is well known for its role in fine-tuning urinary excretion of electrolytes and water. Emerging evidence suggests a potential role played by the CD in immunity and renal injury but the underlying mechanism largely remains elusive. Within the CD, (pro)renin receptor (PRR) via site-1 protease (S1P)-derived soluble PRR interacts with renin controls the intrarenal renin-angiotensin system (RAS) to regulate Na+ and water balance and blood pressure. The present study attempted to employ mouse models of CD-specific deletion of PRR and renin (CD PRR KO and CD renin KO, respectively) and a specific S1P inhibitor PF-429242 (PF) to explore the pathogenic role of this local system in renal injury induced by unilateral ureteral obstruction (UUO). Male 3-4-month-old CD PRR KO and CD renin KO, and their respective floxed controls were subjected to UUO surgery or sham operation for 3 days, followed by analysis of renal fibrosis, inflammation, and indices of the intrarenal RAS. Male 3-4-month-old C57BL/6 mice were subjected to the same surgical procedures and infused with vehicle or PF at 20 mg/kg/day via minipump for 3 days, followed by analysis of the same parameters. 3-day UUO in floxed mice induced renal abundance of fibronectin and α-SMA by 8.6 folds and 5.8 folds, respectively, as assessed by immunoblotting analysis. qRT-PCR detected similar magnitude of increases in mRNA expression of fibronectin, α-SMA, as well as collagen III, collagen I, and TGF-β in the obstructed kidneys. Similar results were obtained by Trichrome Masson staining. In parallel, the obstructed kidney exhibited 4-5-fold increases in renal medullary renin mRNA, renin activity, and active renin content contrasting to unaltered renin levels in the renal cortex. CD-specific deletion of PRR and renin induced comparable attenuation of various indices of renal fibrosis, inflammation, renal medullary renin levels so did PF treatment. UUO induced a 2-fold increase in plasma sPRR, which was completely blocked by PF treatment. Taken together, our results demonstrated that CD PRR/sPRR-dependent activation of renin represents a key determinant of the intrarenal RAS and thus obstruction-induced renal inflammation and fibrosis.
Abstract P378.3: Vigorous Physical Activity And Incident Cognitive Impairment In Hypertension: Findings From The Systolic Blood Pressure Intervention Trial - Memory And Cognition In Decreased Hypertension (sprint Mind) Study
Authors: Kazibwe Richard , Schaich Christopher L , Ahmad Muhammad , Namutebi Juliana H , Epiu Isabella , Hughes Timothy M , Shapiro Michael , Yeboah Joseph
Published: October 2023

Background:
Hypertension has been linked with increased risk of cognitive impairment, but fewer studies have examined the association between physical activity (PA) and incident cognitive impairment in hypertension.

Objective:
To examine the association between vigorous PA (VPA) and incident mild cognitive impairment (MCI), probable dementia (PD), or composite MCI/PD in SPRINT MIND.

Methods:
This analysis included SPRINT MIND participants with baseline self-reported PA data. VPA, defined as PA associated with sweating, increased heart rate or breathing, was grouped into low (<1 sessions/week) or high (≥1 sessions/week) VPA. Using multivariable Cox regression, we examined the association of VPA and MCI, PD and MCI/PD events.

Results:
This analysis included 7,669 participants (aged 70±9 years, 35% women, 59% White)
(Table).
After a median follow-up of 4.4 years, 571, 271 and 761 MCI, PD and MCI/PD events occurred respectively. High VPA, compared to low VPA participants, experienced lower events rates (per 1,000 person-years) of MCI (14.0 vs 19.7), PD (6.2 vs 9.1) and MCI/PD (18.5 vs 19.7). In multivariable Cox regression model, high VPA, relative to low VPA, was associated with lower risk of MCI (HR [95% CI]: 0.77 [0.64 – 0.92]), PD (0.72 [0.55 – 0.93]), and MCI/PD (0.77 [0.66 – 0.90])
(Figure).
There were no significant interactions between VPA participation status and trial randomization to standard (goal systolic blood pressure (SBP) <140 mm Hg) or intensive (goal SBP <120) treatment for hypertension for any cognitive impairment outcomes.

Conclusion:
Among patients with high-risk hypertension, doing vigorous PA ≥ 1 sessions/week may be protective against cognitive decline.
Abstract P380: Impact Of The Smoking Paradox On Outcomes Of Hypertensive Emergencies
Authors: Muhyieddeen Amer , SALEH KHALED , Abdullah Khaled M , Rasheed Oune , Ranasinghe Sachini , Nomigolzar Soroush , Chang Joseph
Published: October 2023

Introduction:
The "smoking paradox" is a surprising occurrence wherein smoking appears to offer a protective benefit, leading to enhanced survival rates for particular patient populations. This research seeks to explore the presence of this paradox in patients who were admitted due to hypertensive emergencies across the United States in the initial year of the COVID-19 pandemic.

Methods:
We examined data from the 2020 National Inpatient Sample to identify patients who were primarily admitted due to hypertensive emergency. We used ICD-10 codes to distinguish between those with and without a smoking history. We employed logistic and linear regression analyses and accounted for potential confounders. We deemed the results as statistically significant when the 2-tailed p-value was less than 0.05

Results:
In the year 2020, a total of 1,221,535 admissions were primarily due to hypertensive emergencies. Out of these, 527,559 cases, constituting 43.2%, involved patients with a history of smoking. Once we adjusted for confounding variables, we found that patients with a smoking history who were hospitalized due to hypertensive emergencies demonstrated a reduced risk of in-hospital mortality (aOR, of 0.58, 95% CI of 0.55 - 0.63). They also showed decreased usage of mechanical ventilation (aOR 0.86, 95% CI 0.82 - 0.88), vasopressor therapy (aOR 0.57, 95% CI 0.50 - 0.64), mechanical circulatory support (aOR 0.37, 95% CI 0.28 - 0.49), and hemodialysis (aOR 0.90, 95% CI 0.87 - 0.94).

Conclusion:
In summary, patients who have a history of smoking and who are hospitalized due to hypertensive emergencies tend to fare better than those without a smoking history. Further in-depth studies are necessary to fully understand the implications of this smoking paradox on such patients. This would help in revealing any underlying factors and consequently lead to improvements in patient care strategies.
Abstract P381: Impact Of The Obesity Paradox On Outcomes Of Hypertensive Emergencies
Authors: Muhyieddeen Amer , Nomigolzar Soroush , SALEH KHALED , ABDULLAH KHALED , Ranasinghe Sachini , Chang Joseph , Rasheed Oune
Published: October 2023

Introduction:
The "obesity paradox" is a surprising occurrence wherein obesity appears to offer a protective benefit, leading to enhanced survival rates for particular patient populations. This research seeks to explore the presence of this paradox in patients who were admitted due to hypertensive emergencies across the United States in the initial year of the COVID-19 pandemic.

Methods:
We examined data from the 2020 National Inpatient Sample to identify patients who were primarily admitted due to hypertensive emergency. We used ICD-10 codes to distinguish between those with and without obesity. We employed logistic and linear regression analyses and accounted for potential confounders. We deemed the results as statistically significant when the 2-tailed p-value was less than 0.05.

Results:
During the calendar year of 2020, there were a total of 1,221,535 admissions primarily for hypertensive emergencies, of which 282,285 (23.1%), involved patients concurrently diagnosed with obesity. After adjusting for confounding variables, patients hospitalized for hypertensive emergencies, with obesity, demonstrated a decreased in-hospital mortality risk (aOR 0.67, 95% CI 0.63 - 0.73), as well as reduced usage of vasopressor therapy (aOR 0.69, 95% CI 0.60 - 0.79), mechanical circulatory support (aOR 0.33, 95% CI 0.24 - 0.47), and hemodialysis (aOR 0.55, 95% CI 0.53 - 0.58). However, they showed increased use of mechanical ventilation (aOR 1.57, 95% CI 1.52 - 1.63).

Conclusion:
In conclusion, obese hypertensive emergency patients showed reduced in-hospital mortality, vasopressor use, mechanical circulatory support, and hemodialysis initiation, but increased mechanical ventilation use compared to non-obese counterparts. More comprehensive studies are required to comprehend the obesity paradox's impact on such patients, helping to unearth underlying factors, and thereby enhancing patient care strategies.
Abstract P382: Long-term Consequences Of Early Childhood Obesity In The Endothelial And Erectile Function Of Male Rats
Authors: Priviero Fernanda , Moura Kawane , dos Passos Junior Rinaldo R , Townsend Paul , Wilson Emily , Torres Uchoa Ernane , Webb R Clinton C , McCarthy Cam , Wenceslau Camilla F , Ceravolo Graziela
Published: October 2023

The consequences of obesity to endothelial and erectile dysfunction are well documented, however, the consequences of obesity in early childhood in later years are unknown. We hypothesize that early childhood obesity induced by postnatal overfeeding impairs aortic reactivity, erectile function, and blood pressure in prepubertal and adult male rats. At postnatal day (PND) 1, Wistar rats were divided into a normal litter (NL, dams were kept with 5 female and 5 male pups) or small litter (SL, dams were kept with 2 male and 1 female pup). The rats were evaluated at two time points prepubertal (PND 40), and in adulthood (PND 120). Body weight (g) and retroperitoneal adipose tissue (fat pad weight/100g of the body n=9-13) were evaluated. The mean blood pressure (MBP, mmHg n=6-7) was measured in conscious rats by indirect tail-cuff method. Aorta and corpus cavernosum were removed. Vascular function was performed via pin myograph and erectile function via strip myograph. Concentration-response curves to phenylephrine (PE) or acetylcholine (ACh) were performed. Prepubertal SL rats had higher body weight (NL 148±2 vs. SL 185±4, g, p<0.05), and adipose tissue deposition (NL 0.17±0.09 vs. SL 0.32±0.03, p<0.05). SL at PND 120 had higher body weight (NL 419±9 vs SL 462±5, g, p<0.05) and retroperitoneal adipose tissue (NL 1.2±0.9 vs SL 1.6±0.1, p<0.05]), and SL rats presented increased MBP (NL 114.9±0.58 vs SL 120.5±1.20). No changes in endothelium-dependent relaxation were observed in the aorta at PND 40 or 120. However, there was an increase in vascular contractility in SL group at PND 40 (Emax: NL 1.17±0.40 vs SL 1.47±0.06, g, p<0.05). In the corpus cavernosum, the relaxation induced by electrical field stimulation was significantly decreased for all frequencies of stimulation in SL rats at PD120 compared to NL rats (1 Hz: NL 0.77 ± 0.18% vs SL 0.27 ± 0.09%; 4 Hz: NL 2.48 ± 0.26% vs SL 1.36 ± 0.41%; 16 Hz: NL 3.06 ± 0.28% vs SL 2.39 ± 0.53%). Our data suggest that obesity in early childhood can cause long-lasting vascular damage to males that can be associated with erectile dysfunction in adulthood.
Abstract P384: Cytochrome P450 1B1-Testosterone Metabolite 6β-Hydroxytestosterone Promotes Ang II-induced Hypertension And Neuroinflammation Via Group IV Cytosolic Phospholipase A
2
α In Paraventricular Nucleus Of Male Mice
Authors: Song Chi Young , Shin Ji Soo , Singh Purnima , Dutta Shubha R , Malik Kafait U
Published: October 2023

We reported previously that Ang (angiotensin) II-induced hypertension depends on the activation of group IV cPLA
2
α (cytosolic phospholipase A
2
α). Moreover, we showed that testosterone (T) metabolite 6β-hydroxytestosterone (6β-OHT) generated by CYP1B1 (cytochrome P450 1B1) in the paraventricular nucleus (PVN) promotes Ang II-induced hypertension and neuroinflammation in male mice. This study determined the relationship of cPLA
2
α and CYP1B1-T derived 6β-OHT in the PVN to Ang II-induced hypertension and neuroinflammation in male mice. cPLA
2
α knockdown in the PVN by transduction with adenovirus (Ad)-cPLA
2
α-short hairpin (sh)RNA (200 nL, bilaterally, 5.4X10
11
pfu/mL) but not its control Ad-scrambled (Scr)-shRNA (2.5X10
11
pfu/mL) in wild-type (WT) male mice, inhibited Ang II (700 ng/kg/min, s.c., two weeks)-induced increase in systolic blood pressure (Day 12- SBP mmHg, tail-cuff) (126±4 vs 167±4, respectively, P<0.05, n=4/group). Moreover, reconstitution of cPLA
2
α in the PVN by Ad-cPLA
2
α-DNA (5.5X10
9
pfu/mL), but not its control Ad-GFP-DNA (1.0X10
11
pfu/mL) in

cPLA
2
α
-/-

mice restored the increase in SBP (153±6 vs 117±4, respectively, P<0.05, n=4/group). Ang II-induced increase in mean arterial blood pressure (MAP mmHg, radiotelemetry) that was minimized in WT-orchidectomized (ORX) or intact

Cyp1b1
-/-

mice were restored by ICV injections of 6β-OHT (1.5 μg/2 μL/alternate day), but it was attenuated by ICV (2 μL, single injection) Ad-cPLA
2
α-shRNA, but not its control Ad-Scr-shRNA (114±4 vs 150±7, and 121±2 vs 154±9, respectively, P<0.05, n=4-6/group). Ang II-induced increase in MAP was restored by 6β-OHT, but not its vehicle (2-hydroxypropyl-β-cyclodextrin in CSF, 2 μL/alternate day) in Ad-cPLA
2
α-DNA transduced ORX-

cPLA
2
α
-/-

mice (165±6 vs 121±2, respectively, P<0.05, n=4/group). The number of TMEM119
+
microglia and GFAP
+
astrocytes in PVN, markers of neuroinflammation, followed the changes in BP in the above groups produced by Ang II. In conclusion, T-CYP1B1 metabolite 6β-OHT promotes Ang II-induced hypertension and neuroinflammation by a mechanism dependent on cPLA
2
α in the PVN. Therefore, agents that reduce CYP1B1 or cPLA
2
α activity could be useful for treating Ang II/T-dependent hypertension and neuroinflammation in males.
Abstract P391: Cellular Camp Nanoarchtecture-signaling Changes Cause Hypertension With Brachydactyly
Authors: Kayser Charlotte , Leeuwen Lisette , Herkert Johanna C , Vos Yvonne J , Lohse Martin , Luft Friedrich C , Bock Andreas
Published: October 2023

G protein-coupled receptors (GPCRs) control cell functions by responding to a myriad of extracellular signals, such as hormones and neurotransmitters. GPCRs comprise the most important drug targets. Cells express many different GPCRs each eliciting distinct and specific cell functions; however, GPCRs use only a few second messengers such as cyclic adenosine monophosphate (cAMP) to relay precise receptor stimuli. To control cell signaling specificity, we showed recently that cells organize subcellular cAMP signaling in so-called
cAMP nanodomains,
namely nanometer-sized signaling compartments of different local cAMP concentrations. GPCRs orchestrate high-concentration cAMP nanodomains to stimulate cell signaling, whereas phosphodiesterases (PDEs), enzymes that degrade cAMP, control low-concentration cAMP nanodomains to gate cAMP effector activation and downstream signaling. This precise
cAMP signaling nanoarchitecture
is essential for cell homeostasis. HTNB is a Mendelian hypertension form that results in dramatic increases in blood pressure leading to death by stroke at the age of 50 years when untreated. Increased peripheral vascular resistance is responsible. We present an HTNB patient with a novel, single-point mutation (L910P) in the catalytic PDE3A core. The localization indicates a direct influence on cAMP hydrolysis. We developed a FRET-based
in vitro
assay to determine the hydrolytic activities of the disease-causing PDE3 mutant to be 3-fold higher than PDE3A wt (V
max
(nM (cAMP)/s) were 143±7 and 45±3, respectively), substantially greater than earlier mutants we described. We used our recently developed
nanoruler imaging technology
for cAMP and downstream effectors and found that the increased cAMP turnover leads to pathologically large low-cAMP nanodomains in vicinity of PDE3A, thereby altering downstream cAMP signaling. Our data suggest that altered cAMP signaling, at the nanometer scale, causes the hypercontractile vascular smooth muscle phenotype and increased peripheral resistance in HTNB, since local protein kinase-A (PKA) activity is hypoactive in the PDE vicinity. We propose that disrupted cellular cAMP-signaling nanoarchitecture forms the molecular basis for HTNB.

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Abstract P395: Clozapine Treatment For Schizophrenia May Cause Salt-sensitive Hypertension By Reducing The Expression Of The Renal Dopamine D4 Receptor
Authors: Xu Peng , Gildea John J , Marino Collin F , Parrott Quay W , Carson M. Chase , Kelly Deanna L , Felder Robin A
Published: October 2023

Clozapine (CLZ) is the most effective antipsychotic for treatment-resistant schizophrenia which affects approximately 24 million people worldwide. Schizophrenics are 3-4 times more likely to die from cardiovascular disease due to increased incidence of hypertension. CLZ is a high affinity antagonist for the dopamine type 4 receptor (D
4
R). Studies have shown that germline deletion of D
4
R in mice caused hypertension, and CLZ administered subcutaneously in mice induced hypertension. Since the proximal tubule (PT) regulates about 75% of excreted Na
+
we cultured renal proximal tubule cells excreted in the urine (uRPTCs) from individuals treated with and without clozapine and previously found that CLZ decreased D
4
R recruitment to cell surface and increased reactive oxygen species in healthy controls (HC). Recently, western blot analysis showed D
4
R expression was reduced in CLZ treated patients (CLZ 0.85±0.08 n=12 vs HC 1.09±0.09 n=11, p<0.05 t-test). The total D
4
R protein was also decreased under CLZ treatment in RPTCs from HC. This suggests that the reduction in D
4
R occurred in PTs when treated with CLZ in-vivo but this was a durable effect still measurable through the process of culturing the cells, and is replicated in-vitro using healthy control cells. In In-vivo CLZ treated patient cells, D
4
R expression is not further reduced when treated in-vitro. Moreover, the natriuretic dopamine D1 receptor (D
1
R) was significantly increased under ClZ treatment of uRPTCs from HC, but not RPTCs from CLZ treated patients (VEH 0.37±0.07 vs CLZ 0.5±0.08 n=11, p<0.05 paired t-test; CLZ/VEH, HC 1.51±0.18 n=11 vs CLZ 0.99±0.01 n=12, p<0.05 t-test). Interestingly, high salt (HS) treatment on these uRPTCs showed a similar trend with CLZ treatment (VEH 0.33±0.06 vs CLZ 0.47±0.08, n=10, p<0.05 paired t-test; HS/VEH, HC 1.55±0.29 n=11 vs CLZ 0.99±0.01 n=12, p<0.05 t-test), indicating these CLZ treated patients may have a blunted dopamine response to excess sodium and therefore develop salt sensitive hypertension. In Summary, CLZ induced hypertension in these schizophrenia patients may be caused by a disrupted dopaminergic system. Further investigations also need to be done including response of sodium transporters and modulation of the renin-angiotensin system.
Abstract P403: Prevalence And Incidence Of Dyskalemia In Adults With Hypertension Initiating Fixed-dose Combination Treatment Of Telmisartan And Amlodipine In Bangladesh: Findings From The OK Study
Authors: Ishigami Junichi , Hasan Md. Mahmudul , Sarker Aruna , Nahar Sharmin , Shuvo Md. Sibly Sadik , Ishraquzzaman Mir , Al Mamun Mohammad Abdullah , Kalimuddin Md. , Sobhan Sheikh Mohammad Mahbubus , Zhao Di , Matsushita Kuni , Appel Lawrence J , Choudhury Sohel Reza , Miller Edgar R , Malik Fazila-tun-nesa
Published: October 2023

Introduction:
WHO recommends fixed-dose combination (FDC) pills for treating hypertension. All FDC pills include renin-angiotensin inhibitor (RASi) or diuretics and are considered to require blood tests for checking dyskalemia, a significant barrier for implementation in resource-limited settings. However, the need for blood tests may be overemphasized if dyskalemia is uncommon.

Methods:
In 2022-2023, a community-based screening program in Dhaka, Bangladesh, recruited adults who were candidates for hypertension treatment (SBP ≥140 and/or DBP
>
90 mmHg). We examined the prevalence of dyskalemia, and of those free of prevalent dyskalemia, the incidence of dyskalemia at 2 months of initiating a daily FDC of telmisartan 40mg and amlodipine 5mg. Secondary outcomes were BP change, medication adherence, and symptoms.

Results:
Of 1,075 participants (mean age 54 yrs, 71% men, mean baseline BP 157/94 mmHg), hypo- (K <3 mmol/L) and hyperkalemia (>5 mmol/L) were present 1.6% each. Of 1,017 patients without hyperkalemia or creatinine clearance <30 who initiated FDC, 866 had the follow-up blood test. The incidence of hypokalemia (K<3) and hyperkalemia (>5.5) was 1.5% and none, respectively (Figure). Mean SBP change was -29.8 mmHg, 92% self-reported taking the medication every day, and 1% self-reported mild symptoms (e.g., leg swelling). There was one death of undetermined cause.

Conclusions:
In Bangladeshi adults with hypertension, the prevalence of dyskalemia was 3.2%. Of those who initiated FDC of telmisartan and amlodipine, 1.5% developed incident hypokalemia and none developed hyperkalemia. Our study suggests that this FDC can be safely used without follow-up blood test.
Abstract P410: A Novel Method For The Analysis Of Renal Sympathetic Nerve Activity From Multi-fiber Nerve Recordings
Authors: Rodionova Kristina , Veelken Roland , Cordasic Nada , Hilgers Karl F , Schmieder Roland E , Schiffer Mario , Amann Kerstin , Ditting Tilmann
Published: October 2023

Introduction:
Measurement of renal sympathetic nerve activity (RSNA) via bipolar electrodes from multi-fiber preparations in various species has been used for decades in the context of autonomic regulation research. Traditionally, raw neurograms are usually integrated over short time intervals and this approach works perfectly for the analysis of dynamic RSNA changes due to acute intervention. However, comparability of baseline activities between groups is limited. We present a novel analysis method, based on the raw neurogram sampled at rate of 25 kHz.

Material and methods:
For RSNA-burst analysis a software based programmable algorithm was used. Continuous activities longer than three single spikes (i.e., >8ms) were defined as bursts, followed by silent periods with some single spikes. Approximately 10.000 bursts/rat were analyzed and burst amplitude, burst duration, burst area (i.e., duration integral), as well as the burst frequencies were analyzed.

Results:
In rats with myocardial infarction (n=11) we found no difference in integrated baseline RSNA as compared to controls ((n=10). However, the new method revealed higher higher burst rate per cardiac cycle [CC] (2.65 ± 0.39 vs. 1.61 ± 0.38 bursts/CC; P<0.001) and burst frequency (15.09 ± 2.42 vs. 8.52 ±1.54 Hz; P<0.001) compared to healthy controls, indicating increased RSNA.

Conclusion:
Our new method of RSNA baseline analysis was able to detect subtle differences between groups of animals that could not be detected by the traditional method of integrated RSNA analysis. Furthermore, this method has the potential to give further insights into RNSA patterns and synchronization to afferent regulatory input form the kidney itself or other organs.