bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P117: Successful Comprehensive Management of Labile Severe Hypertension With Zero-Salt Diet, Stress Reduction, and Antihypertensive Combination of Sacubitril-Valsartan and Nebivolol
Authors: Swan Alexander M , Kyaw Htet Htet , Aung Htun Min , Thida Aye Mon , Swan Tracy T , Tun May Thu , Swan Alexander Myint
Published: September 2019

Background:
The management of labile severe hypertension under current treatment guidelines of better blood pressure control is often of limited use and unsuccessful. We herein report the success of a different treatment approach combining antihypertensive agents, a zero-sodium diet, and stress reduction.

Methods and Results:
A 66-year-old African-American woman with labile severe hypertension of over 19 years was successfully treated by a comprehensive method, which included a multiple drug regimen of nebivolol, sacubitril, and valsartan. She presented to our clinic with an asymptomatic blood pressure (BP) of 220/120 mmHg with multiple comorbidities such as chronic kidney disease, anemia, hypercholesterolemia, dementia, osteoporosis, and diabetes. She had previously been treated with several antihypertensive medications, which had not only been unsuccessful but had also resulted in symptomatic fluctuations of her SBP between 220 and 110 mmHg along with orthostasis symptoms such as dizziness (resulting in frequent falls due to imbalance) and weakness. She had previously been on enalapril and amlodipine. We started treating her on a zero-salt diet, stress reduction therapy with continuous breathing awareness training and escitalopram. We administered combination antihypertensive therapy utilizing lisinopril, carvedilol, Irbesartan, and nebivolol. Escitalopram therapy resolved her stress-related, anxiety-induced high BP from SBP 220 to 180 mmHg. Successful step-wise reductions in her BP to 110/70 mmHg without orthostasis occurred as a result of a step-up fashion titration of sacubitril-valsartan and nebivolol over a three-month period.

Conclusion:
We successfully treated severe labile hypertension, which was resistant to previous treatment, by combining: (1) a zero-sodium diet; (2) behavioral modification with stress reduction therapy; and (3) a combination of sacubitril-valsartan and nebivolol. The combination of sacubitril-valsartan and nebivolol was more effective than any other antihypertensive medication combination. Although sacubitril-valsartan is indicated for the management of heart failure, it controlled BP very well and, by gradual titration, allowed the patient to reach a lower BP in a step-wise fashion.
Abstract P118: Angiotensin-(1-7) Improves Cardiometabolic Function in Aged Mice
Authors: Miller Amanda J , Bingaman Sarah S , White Melissa C , Arnold Amy C
Published: September 2019

Background:
Aging is associated with impaired cardiometabolic function including insulin resistance, elevated blood pressure, and cardiac hypertrophy. Angiotensin (Ang)-(1-7) is a beneficial hormone of the renin-angiotensin system that improves control of blood pressure and glucose homeostasis in cardiovascular disease models in young mice. To our knowledge, no studies have evaluated the importance of Ang-(1-7) to integrated cardiometabolic function in aging. We hypothesized that Ang-(1-7) would improve insulin sensitivity and decrease blood pressure in healthy aged mice.

Methods:
Sixteen month-old male C57BL/6J mice received 6-week Ang-(1-7) [400 ng/kg/min, n=9] or saline (n=9) infusion via subcutaneous osmotic mini-pumps. All mice were fed standard chow diet (18% kcal from fat). During the last week of treatment, intraperitoneal insulin and glucose tolerance tests were performed. Body composition was measured by nuclear magnetic resonance imaging and blood pressure was measured via carotid artery catheter connected to a strain-gauge transducer and blood pressure analyzer. Heart weight and heart: body weight ratio was determined at the end of experiments.

Results:
Ang-(1-7) did not alter body mass [Ang-(1-7): 48.7±2.0 g, saline: 46.1±1.6 g,
p
=0.339] or body composition. Ang-(1-7) improved insulin sensitivity [Ang-(1-7): -2896±593 AUC, saline:-1171 ± 624 AUC
, p
=0.033] but did not affect fasting glucose levels [Ang-(1-7): 180±5 mg/dL, saline: 169±8 mg/dL,
p
=0.225] or glucose tolerance (
p
=0.202). Ang-(1-7) also decreased systolic [Ang-(1-7): 105±2 mmHg, saline: 116±4 mmHg,
P
=0.031] diastolic [Ang-(1-7): 77±2 mmHg, saline: 83±2 mmHg,
P
=0.041], and mean [Ang-(1-7): 86±2 mmHg, saline: 94±3 mmHg,
P
= 0.023] blood pressure. Furthermore, Ang-(1-7) reduced heart weight [Ang-(1-7): 0.18±0.01 g; saline: 0.21±0.01 g,
P
=0.038] and heart to body weight ratio [Ang-(1-7): 0.004±0.001; saline: 0.005±0.001,
P
=0.049].

Conclusions:
Chronic Ang-(1-7) treatment improves insulin sensitivity, lowers blood pressure, and attenuates cardiac hypertrophy in aged mice even in the absence of effects on body weight or composition. These data suggest Ang-(1-7) may provide a novel pharmacological target to improve age-related cardiometabolic disease.
Abstract P119: Prevalence and Coincidence of Arterial Hypertension and Orthostatic Hypotension in Pre and Centenarians: Preliminary Results of Moscow Centenarian Study
Authors: Eruslanova Kseniia , Runichina Nadejda , Kotovskay Julia , Tkacheva Olga
Published: September 2019

Background:
Orthostatic hypotension (OH) and Arterial Hypotension (AH) is commonly reported among older adults and is associated with an increased risk of mortality. The number of centenarians is, but they are still under-investigated population. The aim of the Moscow Centenarian Study (NCT02876809) was to perform a complex evaluation of centenarians living in Moscow. Preliminary results on arterial hypertension and orthostatic hypotension prevalence and blood pressure levels are reported in this abstract.

Methods:
Data was collected 82 participants aged 95 years and older (median 98 y.o) who participated in the Moscow centenarian study in 2016. Face-to-face interviews were conducted and data collected include blood pressure (BP) measurements and medical history.

Results:
The prevalence based on blood pressure measurements of AH was 78.1%. However, 2% were unaware of their high BP. Average supine systolic blood pressure (SBP) was 151 mmHg (with the range between 100 and 216 mmHg) and diastolic blood pressure - 74 mmHg (with a range between 44 and 197 mmHg). 33.8% had SBP between 140-159 mmHg, 17.6% - 160-179 mmHg and 22% had SBP equal or above 180 mmHg. Average supine DBS was 74 mmHg. 4.4% had DBP 50 mmHg or below, 22% - 90 or above mmHg. 80% of the patient took medication for AH. In average older adults took 2 medications to control blood pressure, 17% did not take any pills for hypertension.The prevalence of OH among pre- and centenarians in Moscow was 24.3% (29.2% were bad binders, and 46.1% did not have orthostatic hypotension). 95.6% who had OH took medication to control BP. The mean number of drugs was 2.The coincidence of AH and OH was 18.3%. However, 4.9% had isolated OH, and 21.4% had AH without evidence of OH.

Conclusions:
The coincidence of AH and OH are common in pre and centenarians and reach almost 20%. The preliminary results of the Moscow centenarian Study demonstrate wide ranges of systolic and diastolic BP in centenarians. BP impact on physical status and cognitive functions should be evaluated for a better understanding of health status in centenarians.
Abstract P123: Traditional Chinese Herbal Qian Yang Yu Yin Granules Treat Renal Damage in Spontaneously Hypertensive Rats by Inhibiting Renal Fibrosis
Authors: Fang Yuan , Ding Kang , Fang Zhuyuan , Wang Han , Zhang Biao
Published: September 2019

Background:
Qian Yang Yu Yin Granules (QYYYG) is a Chinese herbal formula. It has been used in the clinical treatment of hypertensive renal impairment for more than 30 years. The pilot study curative effect is distinct.

Methods:
We elucidated the mechanisms underlying the therapeutic benefits of QYYYG, validate the drug-target predicted by the systems pharmacology analysis. WKY as control group. SHR were randomly divided into 3 groups: SHR, SHR+ Valsartan(0.03g/kg/d) and SHR +QYYY(5g/kg/d). WKY and SHR were gavage by distilled water. ELISA detected renal damage, tubular injury and fibrosis markers. HE and Masson staining to observe the general view and fibrosis degree.

Results:
After 4 weeks treatment, QYYYG reduced the levels of blood pressure and the expression of mALB, α1-MG, β2-MG, NGAL, KIM-1 and IL-18. HE staining of SHR kidneys showed classical pathological lesions including accumulation of extracellular matrix, infiltration of inflammatory cells and apparent interstitial fibrosis where renal fibrosis. These pathologic changes were reversed by QYYYG. The serum levels of LN, HA, pro-Col III and Col IV was also decreased. Similar results were found with Masson staining. RT-qPCR selected confirmed the reduced expression of TGF-β and the downstream fibrotic genes, closely associated with EMT in renal fibrosis. Overall, the therapeutic effects of QYYYG on renal fibrosis were consistent with those predicted by pathway analysis.

Conclusions:
Network-based analyses such as those described here may contribute to the holistic understanding and pharmacological evaluation of herbal remedies. QYYYG was validated as an effective treatment for hypertensive renal fibrosis.
Abstract P126: Statines Reduce Cardiac Dysfunction After Preeclamptic Pregnancy
Authors: Kraeker Kristin , Schuette Till , Herse Florian , Golic Michaela , Birukov Anna , Mueller Dominik N , Dechend Ralf , Haase Nadine
Published: September 2019

Introduction:
Former preeclamptic women have an increased risk of cardiovascular disease in later life. However, the underlying functional and structural mechanisms are still unknown.

Objective:
We tested the hypothesis that pravastatin has a beneficial effect on the remodeling of the maternal heart after preeclamptic pregnancy and thus reduces the long-term cardiovascular risk.

Methods:
Female rats harboring the human angiotensinogen gene [TGR(hAogen)L1623] developed a preeclamptic phenotype during pregnancy when mated with male rats carrying the human renin gene [TGR(hRen)L10J], but behaved physiologically normal postpartum. To investigate a possible intervention, we treated preeclamptic dams with pravastatin for four weeks after birth, which was started already during pregnancy. Cardiac structure and function was compared by speckle tracking echocardiography, gene expression analysis, and immune staining of the maternal heart.

Results:
Due to pravastatin treatment, former preeclamptic rats reduced signs of cardiac hypertrophy (perimeter cardiomyocytes 65.3±0.3 vs. 60.5±0.5 μm), fibrosis (fibronectin 3.9±0.3 vs. 1.8±0.2 %) and improved cardiac microcirculation (CD31+ cells 219.0±4.7 vs. 269.1±8.6). In addition, cardiac output was increased postpartum by statin treatment (ejection fraction 57.2±1.2 vs. 61.0±1.9; global longitudinal strain -14.5±0.6 vs. -19.8±1.0 %; heartrate 355.0±8.7 vs. 328.6±8.3 bpm). Analysis of maternal blood serum showed a reduction of brain natriuretic peptide (BNP 0.39±0.05 vs. 0.33±0.01 ng/ml) and soluble fms-like tyrosine kinase 1 (sFlt1 0.69±0.02 vs. 0.51±0.02 ng/ml) even four weeks after birth. Fetuses at the time of birth also benefited from treatment (brain liver ratio 0.93±0.03 vs. 0.82±0.01; heart body ratio 7.14±0.09 vs. 6.80±0.12).

Discussion:
Former preeclamptic rats showed significant cardiac hypertrophy in combination with fibrosis and capillary rarefaction. These irreversible structural changes can be reduced by pravastatin treatment. We could not detect any harmful influence of statins on the fetus.
Values mean±SEM, PE vs. PE+pravastatin
Abstract P130: Renal Endothelin-1 Contributes to Salt Sensitivity in Male Sprague-Dawley Rats Under High-Fat Conditions
Authors: Soliman Reham H , Jin Chunhua , Taylor Crystal M , Pollock David M
Published: September 2019

Decreased renal medullary endothelin-1 (ET-1) has been attributed to salt sensitive (SS) hypertension. Diet induced obesity is associated with SS, but the role of ET-1 is not clear. Our overarching hypothesis is that high fat (HF) diet produces renal ET-1 dysfunction. Male Sprague-Dawley (SD) rats maintained in 12:12 light:dark conditions were put on either 45 Kcal% fat (high fat, HF) or 10 Kcal% fat (normal fat, NF) diet starting at 6 weeks of age for 8 weeks duration. Half-way through the feeding protocol, rats were implanted with telemetry transmitters for blood pressure (BP) measurement. For the last 2 weeks of feeding, HF and NF groups were divided into 2 subgroups to receive an additional high salt (HS) (4%NaCl) diet or continue on the normal salt (NS) (0.3% NaCl) diet. For the last 3 days of the feeding protocol, rats were put in metabolic cages. Rats on HF diet had an impaired active-time acute natriuretic response after intraperitoneal administration of an acute salt load (ΔUNaV was 605 ± 98 vs 960 ± 59 μEq/12 hrs in the first 12 hours post-load, n= 10, p=0.001). HF diet significantly attenuated ET-1 excretion during the active time period compared to NF (0.92 ±0.15 pg/12hrs vs 1.52 ±0.09, n=12, p=0.0007). Rats on NF given HS, had a significant increase in urinary ET-1 excretion compared to NS (4.34 ±0.35 vs 1.65 ±0.38 pg/12hrs, n=4, p=0.0003). However, HS diet failed to increase ET-1 excretion in rats on HF (1.32 ±0.12 vs 2.56 ±0.29 pg/12 hrs, NS vs HS, respectively, n=6, p=0.10). HF significantly increased systolic BP compared to NF after 6 weeks (141 ±2 vs 134 ±2 mmHg, n=10, p=0.01). HS led to a further increase in active-time systolic BP in the HF group compared to NS (149 ±2 vs 143 ±0.5 mmHg, n=6, p=0.04), while addition of HS to the NF group showed no significant increase in systolic BP (142 ±3 vs 134 ±4 mmHg, n=4, p=0.2) during the active period. Thus, we observed that 1) HF diet impairs the natriuretic response to an acute salt load, that is associated with impaired ET-1 excretion, and 2) HF diet induced SS hypertension in SD rats. Given the importance of ET-1 in the renal response to high salt, these findings are consistent with our hypothesis that reduction in renal endothelin-1 contributes to salt sensitivity in HF male SD rats.
Abstract P135: Angiotensin II, But Not Methoxamine Or 5-HT, Causes ATP Release in the Rat Mesenteric Arterial Bed
Authors: Kummer Katherine A , Wilken Gerald H , Macarthur Heather
Published: September 2019

The control of vascular caliber relies on mediators released from multiple components of the vascular neuroeffector junction. These mediators include ATP, which is released from the sympathetic nerves from vesicles that also contain norepinephrine, as well as from the vascular smooth muscle (VSM) via pannexin-1 (panx-1) channels. We hypothesize that VSM-derived ATP plays a critical role in balancing the vasoactive effects of mediators at the vascular neuroeffector junction.

Panx-1 channel opening on VSM has been reported to be stimulated by caspase cleavage, cytoplasmic Ca
2+
, and extracellular K
+
, but the effects of VSM GPCR activation are not as well characterized. Here we utilize a near-real time luminometric technique to quantify the release of ATP from the rat mesenteric arterial bed in response to vasoconstrictor agonists. We observed disparate effects of three physiologically relevant vasoactive agents, and these do not correlate with the relative changes in perfusion pressure. Whereas angiotensin II caused a robust release of ATP (228.6 ± 31.94 nM), no significant release was observed with either methoxamine (an α
1
agonist; 44.41 ± 31.94 nM) or 5-HT (0 ± 0 nM) . These results indicate that GPCR-mediated smooth muscle contraction is not sufficient to induce ATP release in this vascular bed.

This is an important first step toward understanding the role of ATP in the vasculature.
Abstract P136: Comparison of Pharmacy Refill Data With Therapeutic Drug Monitoring (TDM) in Assessing Non-Adherence to Cardiovascular Drugs in Patients With Uncontrolled Hypertension
Authors: Wu Bryan , Sharma Shishir , Lodhi Hamza , Schesing Kevin , Das Sandeep , Brown Nancy , Moss Elizabeth , Halm Ethan , Vongpatanasin Wanpen
Published: September 2019

Pharmacy refill data are frequently used to screen for medication non-adherence in clinical practice but its accuracy has not been validated against therapeutic drug monitoring (TDM) in patients with uncontrolled hypertension. Accordingly, we evaluated the accuracy of proportions of days covered (PDC) and medication possession ratio (MPR) in assessing non-adherence to cardiovascular medications against therapeutic drug monitoring (TDM) in patients with uncontrolled hypertension at outpatient clinics of Parkland Memorial Hospital. Patients who had blood pressure of >130/80 mmHg, were on ≥2 antihypertensive medications, and verbally reported full medication compliance were enrolled in the study after an informed consent. Plasma samples were obtained for measurement of 36 cardiovascular drugs including statins, using liquid chromatography mass spectrometry assay. Among 38 patients enrolled in our study, 21% (8/38 patients) were non-adherent to at least 1 antihypertensive medication, while 39% (12/31 patients) were non-adherent to statin drugs. The non-adherent patients were younger than the adherent patients (57.2±12.0 vs. 62.9±7.8, p=0.08), and were less likely to be African Americans (7/17 vs. 16/21, p<0.05). The non-adherent group to statin drugs had significantly higher LDL level than the adherent group (112±41 vs. 70±21 mg/dL, p<0.04). The adherent group to antihypertensive medications had similar blood pressures as the non-adherent group (145±12.8/82±9.8 vs.146±9.6/87±12.9 mmHg). The pharmacy refill data are available in 50% (19/38) of patients, and there was no significant correlation between PDC/MPR and TDM results (r
2
=0.15, p=0.11 for PDC; r
2
=0.15, p=0.16 for MPR). Using a threshold of < 80%, low PDC has a sensitivity of 100% and a specificity of 63% in detecting medication non-adherence when compared to TDM. Similar results were obtained for MPR: sensitivity of 100% and specificity of 65%. While medication refill data may be a sensitive screening tool for medication non-adherence, it has limited specificity and availability when compared to TDM. Thus, TDM constitutes a more efficient and reliable way to assess medication non-adherence, which is crucial in optimizing cardiovascular risk factors in this indigent population.
Abstract P138: Perivascular Adipose Tissues (pvats) Home Distinct 'Active' Immune Cell Niches, Denser Than Non-pvat Adipose Tissues of Healthy Rats
Authors: Kalyana Kumar Ramya , Rockwell Cheryl E , Watts Stephanie W
Published: September 2019

Perivascular adipose tissue (PVAT) is protective and reduces the contraction of blood vessels in health. Eosinophils are one of the key players to the anti-contractile nature of PVAT in health. This finding led to our hypothesis that an ‘active’ immune complement exists in healthy PVAT. Male and female Sprague Dawley rats (12-14 weeks age) were used. PVATs from the thoracic aorta (brown APVAT), mesenteric resistance vessels (white MRPVAT), non-PVATs: subscapular (brown SS fat), retroperitoneal (white RP fat) and spleen (positive control) were harvested from each animal. T cells (CD4 and CD8), B cells, NK cells, macrophages, mast cells and neutrophils in the stromal vascular fraction were quantified using 9-color flow cytometry. Activation status (effector/ memory/ regulatory) of macrophages, T and B cells were also determined by flow cytometry. The number of immune cells are normalized to tissue weight (table). MRPVAT has denser total immune population (both sexes) and active macrophage pool (females) vs RP fat. APVAT homes a denser immune niche (females) and active T cell, B cell pools (both sexes) vs SS fat. This is the first study to characterize ‘active’ immune populations in healthy PVATs vs non-PVATs in male and female rats. Further studies to understand the functions of basally active immune cells in healthy PVATs are warranted.
Abstract P140: The Role of Pumpkin Flesh in Reducing Mean Arterial Pressure in a Genetic Rat Model for Hypertension
Authors: Thomas Soweto
Published: September 2019

Objective:
ACE inhibitors (ACEi) remain the most commonly prescribed medication; lowering blood pressure, increasing bradykinin levels and decreasing cardiac hypertrophy. A demographic-specific bradykinin sensitivity renders African-American patients on ACEi with elevated risk of angioedema. This increased risk has led a search for natural ACEi from functional foods or natural resources, one of which being pumpkin. In Sprague Dawley rats with L-NAME induced hypertension, pumpkin seed oil significantly reduced systolic blood pressure. As a promising source of β-carotene, phenolics and a beneficial fatty acid profile, this study aimed to examine the potential of pumpkin flesh and seed in regulating blood pressure management in a genetic model for hypertension.

Methods:
Spontaneously Hypertensive Rats (SHR) and Wistar-Kyoto rats (WKY), aged 6 weeks, were fed one of the following diets for 8 weeks: 4% pumpkin flesh (PF), 4% pumpkin seed (PS), control diet (Ctrl), and an SHR-Captopril treated group (Cap). Non-invasive blood pressure monitoring was employed for weekly measuring of mean arterial pressure (MAP). Upon 8 weeks of treatment, animals were euthanized for structural analysis of cardiac hypertrophy (Heart weight to tibial length ratio). Left ventricular mRNA expression of ANP and BNP was quantified using quantitative RT-PCR techniques.

Results:
At 8 weeks, MAP in SHR-PF and SHR-PS groups was significantly reduced by 23% (p=0.0135) and 27% (p=0.0018) respectively, compared to SHR-Ctrl. Heart weight ratios showed no significant difference between SHR-Ctrl and SHR-PF or SHR-PS, while SHR-Cap heart weight significantly decreased by 15% (p=0.0028) in comparison to SHR-Ctrl. Additionally, increased mRNA expression of both ANP and BNP was observed in the SHR-PF group in comparison to WKY-Ctrl.

Conclusions:
The reduction of blood pressure observed in response to pumpkin-based diets suggests an alternative pathway of blood pressure control independent of ACE inhibition. This potential new pathway elucidates the health promoting capabilities of pumpkin as an alternative blood pressure treatment for all demographics.
Abstract P141: Toll Like Receptor 4 Mediated Autophagy Contributes to Hypertension-Induced Kidney Injury
Authors: Majumder Suravi , Pushpakumar Sathnur B , Weber Gregory , Sen Utpal
Published: September 2019

Hypertension is the second leading cause of chronic kidney disease in the world. Angiotensin II (Ang II) induced Toll-like receptor 4, TLR4, activation contributes to hypertension-induced renal inflammation and fibrosis. Recently, we showed that mice with dysfunctional TLR4 are protected from renal injury by reducing inflammation and oxidative stress. Autophagy is a protective mechanism that degrades protein aggregates and damaged organelles to maintain intracellular homeostasis and cell integrity. Consequently, defective autophagy in the kidney can lead to cellular injury. A growing body of evidence implicates altered autophagy to various kidney diseases including hypertension. TLRs are known to play a significant role in autophagy, however, the role of TLR4 mediated autophagy in hypertension induced renal injury remains unclear. We hypothesized that TLR4 deficiency reduces Ang II induced renal injury by suppressing autophagy in hypertensive kidney. C3H/Heouj mice with normal TLR4 and C3H/Hej
LPS-d
with mutant TLR4 (TLR4 deficiency) aged 10-12 weeks were treated without or with Ang II (1000 ng/kg/d) for 4 weeks. In response to Ang II, TLR4 deficient mice showed increased glomerular filtration rate (GFR) (892.43 ± 56.72 vs. 712.63 ± 46.82 μL/min./100g b.w.) and increased renal vascular density and reduced renal cortical resistive index compared to mice with normal TLR4. Ang II treated mice with normal TLR 4 showed increased reactive oxygen species (ROS) generation and upregulation of IκB and NF-kβ compared to TLR4 deficient mice. Ang II increased the expression of autophagy marker proteins, LC3 I/II, p62, Atg5, Beclin1 in the kidney of mice with normal TLR4 compared to mice with TLR4 deficiency. Our data suggests that Ang II induced TLR4 activation upregulates autophagy whereas in C3H/Hej
LPS-d
mice with TLR4 deficiency, autophagy is unaffected and protects the kidney from hypertension injury.
Abstract P144: Integrin β1 in Tubular Epithelium Protects From Acute Injury Induced Fibrosis
Authors: Palamuttam Riya J , Mathew Sijo
Published: September 2019

Acute kidney injury (AKI) results in the sudden loss of renal function primarily due to renal tubular injury. Repeated injury or maladaptive recovery lead to chronic kidney diseases. All forms of chronic kidney disease are characterized by excessive extracellular matrix (ECM) accumulation. The proximal tubule cells that are injured but not detached from the basement membrane are critical for the restoration of renal functions after the injury incidence. Renal tubular epithelial cell adhesion, migration, and proliferation are required for the kidney to recover from sub-lethal injury. These processes require the ability of cells to interact with the ECM. Integrin, which exists as a complex of α and β subunits, are the principal receptors for ECM proteins. Integrin β1 is the major integrin subunit present in kidney and critically regulates renal epithelial cell functions. We investigated the importance of Integrin β1 in kidney proximal tubule epithelial cells. Integrin β1 was deleted from these cells using the γ-gt cre. These KO mice had no morphological abnormalities but have a higher urine osmolality (2369±881 mΩ) compared to WT (2098±945 mΩ). By using a nephrotoxic injury model, we investigated the role of integrin β1 in AKI. Samples were collected on 3, 5, 7 and 14 days after injury to assess the nature of injury and recovery. Integrin β1 KO mice were more susceptible to injury as evident by protein casts and tubule dilation of tubules. The blood urea nitrogen (BUN) from the plasma showed increased BUN level in KO animals compared to WT controls (26.78±8.23 and 34.05±7.11). After the injury the level was increased to 52.26±18.37 in WT and 60.34±11.58 KO suggesting both were injured to a similar extent. After 14 days the WT recovered better than KO animals (BUN 37.33±10.12 and 48.73±15.92). After 14 KO mice had more collagen deposition compared to WT animals. This data suggests the importance of integrin β1 in the tubular epithelium in promoting the recovery from injury and preventing its progression to chronic kidney disease.
Abstract P153: Early Changes in Left-Atrial and Left-Ventricular Geometry and Function in Women After Preeclampsia as Detected by Cardiac Magnetic Resonance Imaging
Authors: Birukov Anna , Funk Stephanie , Balogh Andras , Markó Lajos , Golic Michaela , Rakova Natalia , Wilck Nicola , Blaszczyk Edyta , Lim Carolin , Weiss Sara , Daub Steffen , Kräker Kristin , Haase Nadine , Müller Dominik N , Herse Florian , Schulz-Menger Jeanette , Dechend Ralf
Published: September 2019

Objectives:
Preeclampsia (PE), the leading cause of maternal and neonatal morbidity and mortality, is associated with an increased long-term risk for cardiovascular disease (CVD). We aimed to characterize myocardium and investigate potential functional and structural cardiac alterations in asymptomatic women after PE using cardiovascular magnetic resonance (CMR) imaging.

Methods and Results:
We performed a post-pregnancy case-control study (clinicaltrials.gov ID: NCT03313063). In total, 22 cases and 23 controls were recruited. Participants were matched by age, BMI and parity. Hemodynamic and morphologic characteristics of the myocardium were assessed using established and innovative CMR technics as parametric mapping, late gadolinium enhancement (LGE) imaging and tissue-tracking. Increased left-atrial end-diastolic volume (LA-EDV normalized to BSA: 37.69±6.83 vs. 32.85±6.28, p=0.02) and stroke volume (LA-SV normalized to BSA: 22.57±5.83 vs 18.96±5.10, p=0.02) with a slight tendency to left-ventricular hypertrophy (LV-SV normalized to BSA: 47.28±7.03 vs. 51.58±6.32, p=0.04, LV remodeling index: 0.59±0.11 vs. 0.53±0.08, p=0.045) were found in the post-PE group. Associations between history of PE and changes in LA dimensions remained even after adjustment for BMI, age, parity, DBP, smoking status and years postpartum (adj. β-coefficient for LA-EDV [95% CI]: 9.14 [1.47; 16.81], adj. β-coefficient for LA-SV [95% CI]: 6.74 [0.77; 12.70]). Global circumferential (GCS) and radial (GRS) stains were significantly reduced in post-PE women (-18.28±2.53 vs. -19.82±2.12 and 30.72±6.99 vs. 35.09±6.73, respectively). We could not detect significant differences in T1 or T2 mapping between the groups or fibrosis in LGE imaging.

Conclusion:
Our findings confirm PE as a risk factor for CVD later in life. Changes in LV and LA dimensions were found as early as 2 years after PE pregnancy. These changes might point toward a manifest end-organ damage following PE in the future. We propose that post-PE women will notably benefit from early cardiovascular screenings.
Abstract P157: Role of P47
phox
in Angiotensin II Induced Cardiac Hypertrophy and Fibrosis in Mice
Authors: Reddy S. Santosh , Agarwal Heena , Jaiswal Anant , Barthwal Manoj Kumar
Published: September 2019

NADPH oxidase mediated ROS production has been recognized to be an important contributory mechanism for hypertension and left ventricular hypertrophy (LVH). However, the regulatory role of NADPH oxidase mediated superoxide production in Angiotensin II (AngII) induced cardiac fibrosis and macrophage infiltration is still elusive. In the present study, we investigated the role of phagocytic NADPH oxidase enzyme system in cardiac remodelling induced by AngII in young adult (2-3 months old) male mice deficient in p47
phox
, a cytosolic subunit of the NADPH oxidase (KO, n=13) and age-matched wild-type littermates (WT, n=9). Animals were infused with AngII pressor dose (1500 ng/kg/min, s.c) or saline via osmotic minipump (Alzet 2002, USA) for 14 consecutive days and then, subjected to echocardiography (VEVO 1100, Canada). Further animals were sacrificed and hearts was harvested for histological studies and gene expression analysis. AngII treatment in WT and KO mice showed prominent alterations in echocardiographic measurements with no changes in E/A, EF and FS. However, KO mice showed aggravated cardiac hypertrophic response (LVAWd: WT, 1.20±0.09 vs. KO, 1.42±0.04, p<0.05; LVIDd: WT, 3.02±0.20 vs. KO, 2.60±0.07, p<0.05; LVPWd: WT, 1.49±0.06 vs. KO, 1.78±0.06, p<0.05). Histologically, AngII infused KO mice also showed increased cardiomyocyte diameter compared to AngII infused WT mice (WT, 388±16.37 vs. KO, 560.3±41.28 μm
2
; p<0.01 respectively). Further, AngII infused KO mice showed elevated immune cell infiltration, which were positive for Mac-3 staining compared to AngII infused WT mice (WT, 2.61±0.32 vs. KO, 4.09±0.44 %; p<0.05). Besides, AngII infused KO mice showed augmented interstitial fibrosis (WT, 11.11±0 0.67 vs. KO, 20.85± 3.63 %; p<0.05), thick collagen fibres deposition (WT, 28.93± 0.94 vs. KO, 37.60± 2.49 %; p<0.05) compared to AngII infused WT mice. Moreover, AngII infused KO mice also showed upregulated gene expression of hypertrophic and fibrotic markers, including Nppa, Nppb, Acta1, Myh6, TGF-β1, collagen (I and III) and α-sma compared to AngII infused WT mice. Together, these data suggest that NADPH oxidase and its subunit p47
phox
play a pivotal role in AngII induced LVH by regulating fibrotic machinery and macrophage infiltration.
Abstract P159: Reversing Ocular Hypertension and Blindness by Hydrogen Sulfide
Authors: Singh Mahavir , George Akash K , Homme Rubens P , Metreveli Naira , Tyagi Suresh C
Published: September 2019

Hyperhomocysteinemia (HHcy) is associated with glaucoma, sphincter-muscle atrophy and retinal artery/vein occlusion, mechanisms are unclear. Results show HHcy as a hallmark of epigenetic dysfunction that leads to decrease in H
2
S, a potent vasoactive transmitter, anti-inflammatory and anti-oxidant. HHcy antagonizes beta-2 adrenergic receptor and decreases Gαs subunit. In addition, HHcy causes reduction in H
2
S by decrease in cystathionine β synthase (CBS) and cystathionine γ lyase (CSE). However, it is unclear whether decrease in H
2
S increases ocular pressure and causes blindness. Central hypothesis of this project is that epigenetic-hypermethylation by DNMTs causes decrease in H
2
S, CBS, CSE and MTHFR that lead to retinal vascular dysfunction causing blindness. Increase in H
2
S mitigates blindness
(Fig. 1).
CBS
+/-
and WT mice fed with/without high methionine diet were administered either PBS or H
2
S donor; GYY 4137. Lysates for key-proteins, glutamate and glutathione were examined. Intraocular pressure (IOP) was monitored; barium sulfate and BSA-FITC angiographies were performed for vasculature/permeability. Vision was tested employing novel object recognition test (NORT) and light-dark box test (LDBT). CBS deficiency with HMD led disruption of metabolism leading to HHcy as reflected by increased Hcy and S-adenosylhomocysteine hydrolase. Unlike CBS, CSE and MTHFR were reduced but compensated by GYY 4137. Oxidative/ER stress was mitigated by GYY 4137 with enhanced GSH. Increased glutamate in CBS
+/-
was prominent than WT and these mice exhibited higher IOP that was lowered by GYY 4137. CBS-deficiency resulted in vision impairment as revealed by NORT/LDBT. GYY 4137 improved CBS
+/-
behavior together with lowering their glutamate. BRB appeared compromised in CBS
+/-
with vessel leakage that was mitigated by GYY 4137 corroborating results for occludin stabilization. Findings reveal that HHcy-induced glutamate excitotoxicity, oxidative damage, ER-stress and permeability can compromise vision and GYY 4137 could serve as a therapeutic agent for ocular hypertension and blindness.
Abstract P161: Inhibition of Progesterone Induced Blocking Factor Causes Clinical Characteristics of Preeclampsia in Sprague Dawley Rats
Authors: Amaral Lorena M , Cottrell Jesse N , Cunningham Mark W , Ibrahim Tarek , Vaka Ramana R , LaMarca Babbette
Published: September 2019

Preeclampsia (PE) affects 5-7% of all pregnancies in the U.S and it is characterized by new onset hypertension in association with progesterone deficiency, elevated natural killer (NK) cells and inflammatory cytokines. Despite being a leading cause of maternal death and perinatal morbidity, the mechanisms responsible for the pathogenesis of PE are unclear. Progesterone is crucial for establishing and maintaining pregnancy and it exerts immune modulatory effects by the lymphocyte-derived protein progesterone induced blocking factor (PIBF). Its immunological effects include inhibition of natural killer (NK) cell activity and can regulate the proinflammatory balance. PIBF has been shown to act through IL-4/TH2, which are reduced during PE and increased during normal pregnancy, however the role of PIBF deficiency in PE pathology is not well examined. Thus, this study was designed to test the hypothesis that PIBF blockade stimulates cytolytic NK cells to cause the symptoms of PE during pregnancy. Rabbit anti-PIBF IgG (0.25, low dose-LD or 0.50 mg/mL, high dose-HD) was administered intraperitoneal on gestation day 15 to normal pregnant Sprague Dawley (NP) rats and on day 18 carotid catheters were inserted and on GD 19 blood pressure and samples were collected. MAP in NP rats (n=7) was 99± 3 mmHg, which increased to 116± 2 in NP+ anti-PIBF LD (n =10) and 113±4 in NP+ anti-PIBF HD (n=4), p<0.05. Neither placental weight nor pup weight was affected by PIBF blockade. Circulating total and cytolytic NK cells were 67± 11 and 0.6 ± 0.2 in NP rats (n=4), which total NK cells decreased to 28±7 in NP+ Anti-PIBF LD and 36±4 in NP+ Anti-PIBF HD while cytolytic NK cells were increased to 2.0±1 in NP+ Anti-PIBF LD and 3.0±1 in NP+ Anti-PIBF HD, p<0.05. Plasma IL-4 and IL-10 levels were 22±5, 25±6 in NP (n=5), which decreased to 6±1, 8±1 in NP+ Anti-PIBF LD (n=6, p<0.05) and 16 ±4, 15±5 in NP+ Anti-PIBF HD (n=4). Plasma TNF-alpha levels were 35±8 in NP, 32±6 in NP+ Anti-PIBF LD and 84±21 in NP+ Anti-PIBF HD. Collectively, our findings demonstrate that PIBF blockade increases inflammation and blood pressure to levels similar to what is observed in PE, thus indicating the importance of progesterone signaling pathways for the maintenance of healthy pregnancy.
Abstract P162: Placental Ischemia During Pregnancy Leads to Impaired Cardiac Function and Global Longitudinal Strain
Authors: Bakrania Bhavisha A , Hall Michael E , Shahul Sajid , Granger Joey P
Published: September 2019

Preeclampsia (PE) is a disorder prevalent in 3-8% of pregnancies, characterized by maternal hypertension and endothelial dysfunction. More recently, it has been shown that preeclamptic women exhibit cardiac dysfunction, impaired global longitudinal strain (GLS), which is indicator of contractility and tissue injury, and increased circulating cardiac troponin I (cTnI), however the underlying mechanisms have not been well studied. The Reduced Uterine Perfusion Pressure (RUPP) model of placental ischemia mimics a PE-like phenotype, including hypertension, endothelial dysfunction and adverse cardiac remodeling. However, whether adverse remodeling translates to impaired cardiac function is not known. The aim of this study was to assess cardiac function in RUPP rats during pregnancy. We tested the hypothesis that placental ischemia in the RUPP rat leads to impaired left ventricular (LV) systolic function and GLS. To address this, all animals underwent comprehensive echocardiography assessment on gestational day (GD) 14. RUPP rats underwent surgery to place silver clips on the abdominal aorta and branches of the ovarian artery to induce placental ischemia. Both the Sham (
n
=10) and RUPP (
n
=10) rats had indwelling carotid catheters placed on GD 18, and blood pressure and echocardiography measurements were made on GD 19. The RUPP group showed significantly increased mean arterial pressure compared to the Sham group on GD 19 (123 ± 3 vs. 97 ± 2 mmHg, P<0.01). RUPP hearts also showed reductions in LV ejection fraction (60 ± 2 vs. 78 ± 2 %, P<0.01) and fractional shortening (46 ± 3 vs. 56 ± 1 %, P=0.05), in addition to cardiac hypertrophy (0.97 ± 0.04 vs.0.91 ± 0.02 g, P=0.02). GLS was decreased in the RUPP group compared to the Sham (-17.89 ± 0.5 vs. -26.31 ± 2.7 %, P=0.02), suggesting impaired contractility and injury, and these data were accompanied by increased circulating cTnI. In conclusion, cardiac dysfunction and impaired cardiac strain is present in the RUPP rat in response to placental ischemia. The implication of these findings is the use of an appropriate animal model to understand the mechanisms of cardiac dysfunction in PE and potentially develop therapeutic options that improve cardiac abnormalities in these patients.
Abstract P163: Masked Uncontrolled Hypertension in Treated Hypertensive Patients Have Heightened Out-Of-Clinic Aldosterone Levels
Authors: Siddiqui Mohammed , Dudenbostel Tanja , Judd Eric K , Oparil Suzanne , Calhoun David A
Published: September 2019

Introduction:
Masked uncontrolled hypertension in treated patients (MUCH) is defined as controlled automated office blood pressure (AOBP) in clinic but uncontrolled out-of-clinic 24-hr ABPM. Previously, we have shown that patients with MUCH have evidence of heightened out-of-clinic sympathetic activity (i.e. catecholamines & metanephrines levels) compared to patients with true controlled hypertension (CHTN).

Methods:
In this prospective evaluation, 185 patients were recruited after having controlled BP readings at 3 or more clinic visits. Patients on mineralocorticoid receptor antagonists were excluded. All the patients were evaluated by in-clinic AOBP, & morning serum aldosterone & plasma renin activity. Out-of-clinic ABPM & 24-hr urine aldosterone were also done. Fifty patients had true CHTN & remaining 57 patients were MUCH.

Results:
The patients identified as having MUCH had significantly higher out-of-clinic levels of urinary aldosterone compared to true CHTN. The two groups did not differ in serum aldosterone, plasma renin activity & aldosterone-renin ratio collected in clinic. In addition, 38.6% of MUCH patients had high out-of-clinic urine aldosterone levels (≥ 12 μg), but normal clinic serum aldosterone levels (<16 ng/dL) & an aldosterone-renin ratio (<30).

Conclusions:
Patients with MUCH have higher aldosterone levels compared to patients with true CHTN. However, there was no difference in serum aldosterone levels between the two groups in clinic. These findings suggest that patients with MUCH likely have higher out-of-clinic sympathetic tone that increases aldosterone, catecholamines & metanephrines levels contributing to their MUCH.
Abstract P169: Renal Denervation Attenuates a Catabolic State in Mice Fed High Salt
Authors: Yamazaki Daisuke , Kitada Kento , Morisawa Norihiko , Fujisawa Yoshihide , Nakano Daisuke , Hitomi Hirofumi , Titze Jens , Nishiyama Akira
Published: September 2019

Introduction:
We recently reported that kidneys accumulate urea as an alternative osmolyte in the renal medulla to concentrate sodium into the urine during high salt intake. This urea-driven water conservation process is coupled with the energy-intensive nature of hepatic urea production, which leads to a catabolic state in mice fed high salt. In this study, we examined the effects of renal denervation on the salt-driven catabolic state since previous studies found that the renal sympathetic nervous system regulates urinary sodium excretion and energy metabolism of some organs such as liver and muscle.

Methods:
Sham-operated (sham) or renal denervated (RDX) male C57/B6J mice were fed on 0.3% NaCl diet with tap water (NS) or 4% NaCl high salt diet + 0.9% NaCl water to drink (HS) for 4 consecutive weeks (ad libitum), followed by 2 weeks of pair-feeding to match energy intake in all groups. We measured daily food intake and body weight, 24 hours urinary sodium excretion, body sodium content, and activity of liver arginase, a urea producing enzyme.

Results:
NS + sham and HS + sham mice showed similar body weight gain (NS + sham: +3.6 ± 0.2, HS + sham: +3.4 ± 0.2 g) during ad libitum feeding although HS significantly increased food intake (NS + sham: 3.1 ± 0.04, HS + sham: 3.3 ± 0.04 g/day). After the pair-feeding, HS mice significantly decreased their body weight (NS + sham: +0.9 ± 0.07, HS + sham: -0.6 ± 0.05 g) and increased liver arginase activity (NS + sham: 3792 ± 322, HS + sham: 5412 ± 499 units/L/tissue), confirming the high salt-induced catabolic hepatic urea production. On the other hand, HS did not increase food intake (NS + RDX: 3.2 ± 0.1, HS + RDX: 3.1 ± 0.01 g/day) and liver arginase activity (NS + RDX: 3599 ± 316, HS + RDX: 3363 ± 369 units/L/tissue) in RDX group. In addition, HS + RDX mice did not show pair feeding-induced body weight loss (NS + RDX: +0.6 ± 0.3, HS + RDX: +0.3 ± 0.3 g). HS + RDX mice did not alter 24 hours urinary sodium excretion (HS + sham: 135 ± 6.3, HS + RDX: 142 ± 13 mmol/d/kg) and body sodium content (HS + sham: 0.15 ± 0.003, HS + RDX: 0.15 ± 0.006 mmol/d/kg) compared with HS + sham mice.

Conclusion:
These findings suggest that renal denervation attenuates the HS-induced body weight loss and catabolic urea production independently of urinary sodium excretion.
Abstract P171: Gut Microbiota-Derived Hydrogen Sulfide is Reduced in Spontaneously Hypertensive Rats
Authors: Donertas Basak , Malphurs Wendi L. , Baekey David M. , Julian David , Zubcevic Jasenka
Published: September 2019

Introduction:
Gut bacteria play a significant role in host homeostasis, and gut dysbiosis has been associated with many conditions including hypertension (HTN). Endogenous hydrogen sulfide (H
2
S) is an important freely-diffusing molecule that can modulate neural, cardiovascular and immune system activity, and circulating levels of H
2
S are reduced in animals and humans with HTN. While most research on the role of H
2
S in HTN has focused on H
2
S produced by host tissues, H
2
S produced by gut bacteria may also enter the host circulation. We investigated whether the spontaneously hypertensive rat (SHR), an established model of HTN, has a disruption in gut bacteria-derived H
2
S production.

Methods:
Bacterial DNA from fecal samples of adult male normotensive Wistar-Kyoto (WKY) and SHR was isolated for 16s bacterial genomic sequencing. WKY and SHR fecal and plasma samples were analyzed for H
2
S levels using modified methylene blue assay. Blood pressures were determined in all rats at several time points using a tail cuff. Data are expressed as mean±SEM, with P<0.05 considered statistically significant.

Results:
We found a significant reduction in the abundance of two H
2
S-producing gut bacteria in the SHR compared to WKY:
Enterobacteriaceae
(1.423e-005±1.056e-005 vs. 0.0002329±7.853e-005, n=6, P<0.05), and
Clostridiaceae
(0.01134±0.00431 vs. 0.06408±0.01416, n=6, P<0.01). This decrease in the H
2
S-producing gut bacteria was also associated with a significant reduction in fecal H
2
S levels (SHR: 0±0.01703 AU vs. WKY: 0.094±0.03385 AU, n=5; P<0.05) and lower plasma H
2
S levels (SHR: 0.3265±0.07817 AU vs. WKY: 0.6850±0.1790 AU, n=2) in the SHR compared to the WKY.

Conclusion:
These results suggest that diminished gut bacterial production of H
2
S may contribute to the reduced H
2
S observed in host circulation in established HTN.
Abstract P174: Incidence of Hyponatremia on Spironolactone in Patients With a Prior Episode of Chlorthalidone-Induce Hyponatremia
Authors: Matanes Faris , Siddiqui Mohammed , Dudenbostel Tanja , Calhoun David , Oparil Suzanne
Published: September 2019

Chlorthalidone and spironolactone are commonly used diuretics for patients with difficult-to-manage hypertension. Hyponatremia is a common adverse effect that results in discontinuing these medications in many subjects. We designed this study to determine the incidence of hyponatremia on spironolactone after developing a hyponatremic episode on chlorthalidone. Electronic health records were searched for patients seen at UAB’s outpatient clinics. Inclusion criteria included: patients who developed hyponatremia (serum sodium <133 mEq/L) on chlorthalidone within 90 days of starting the medication and had a prescription for spironolactone at another time point. The sodium levels were checked for 90 days after starting spironolactone. Exclusion criteria constituted having one of the following: heart failure, liver cirrhosis or adrenal insufficiency based on ICD 10 codes or an estimated glomerular filtration rate (eGFR) of < 30 mL/min/1.73 m2. Preliminary analysis yielded eligible 14 patients. Eight had hyponatremia on chlorthalidone, but tolerated spironolactone well, and 6 had hyponatremia on both diuretics. Females comprised 13 out of 14 (92.9%) of the population. There were no significant differences in age, gender, race, baseline sodium level, sodium level at the hyponatremic episode or eGFR between the two groups. These findings suggest that checking sodium levels frequently for those who had hyponatremia with chlorthalidone and are prescribed subsequently spironolactone is warranted.