bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P040: Pressure Natriuresis In Female Sprague Dawley Rats: Characteristics And Mechanisms
Authors: McFarlin Brandon E , Ralph Donna L , McDonough Alicia A
Published: September 2020

Raising blood pressure stimulates pressure natriuresis (P-Nat).
In males (M)
Sprague Dawley rats (SDR), Na
+
reabsorption (T
Na
) is acutely reduced by retraction of proximal tubule (PT) NHE3 to microvillar base and NaPi2 internalization.
In females (F),
at baseline PT NHE3 is already at microvillar base and NaPi2 is less abundant than in M. We AIM to determine characteristics and mechanisms of P-Nat in F (vs M) rats.

Methods:
Inactin anesthetized F and M SDR (n=5/group) were provoked by vasoconstriction (or sham). Mean arterial pressure (MAP) was recorded via carotid artery, urine collected via bladder, Na
+
transporters’ abundance assessed via immunoblot and localization by immunohistochemistry.

Results (Fig 1A):
Baseline
MAP (mmHg) was lower in F vs. M (91 ± 5 vs.105 ± 3,
P
=0.04) while urine volume (UV) and electrolyte excretion (UNaV, UKV) were similar.
After celiac and mesenteric bed constriction,
MAP rose to 128 ± 3 mmHg in both sexes; UNaV, UV and C
Na
increased 12 to 15-fold in F (all
P
<0.01) vs 6-fold in M (
P
>0.08).
Constriction of abdominal aorta
further raised UNaV in F with less impact in M.

Na
+
transporters

. In F, NHE3 remained at PT microvillar base and NaPi2 was internalized with vasoconstriction. NHE3P (indicating inactivation) abundance increased 29% in F,
P
=0.058. Lithium clearance, measure of volume flow leaving early nephron, increased 9-fold in F (
P
=0.02) vs. 5-fold in M (
P
=0.07). F mTAL NHE3, NKCC2p, and SPAKp (co-transporter kinase) abundances were 22, 24, and 43% lower vs shams (
ANOVA
P
<0.0001).

Summary:
F vs M SDR exhibit more robust P-Nat associated with less T
Na
in early nephron and reductions in PT-mTAL Na
+
transporters, consistent with higher UNaV at any given BP (Fig 1B).
Abstract P052: Mir379 Regulates Klotho-deficiency Induced Cardiomyocytes Apoptosis Through Smur1 Repression
Authors: Chen Kai , Sun Zhongjie
Published: September 2020

Background and Objective:
Klotho
is an aging-suppressor gene.
Klotho
gene deficiency impairs heart function leading to heart failure, but the underlying mechanism remains unknown. MicroRNAs are increasingly recognized to play important roles in cardiomyopathy. The objective of this study is to investigate whether Mir379 regulates Klotho deficiency-associated cardiomyocyte apoptosis.

Methods and Results:
Using inducible Cre-Loxp recombination technology, we first found that kidney-specific deletion of the
Klotho
gene caused heart failure and reduced survival. Using microRNA sequencing analysis, we found that Mir379 may be an important mediator of Klotho deficiency-associated heart failure. In H9c2 heart cells, we found that Klotho-free medium induced apoptosis and increased Mir379 levels. To test whether Mir379 mediates Klotho deficiency-associated apoptosis, H9c2 cells were transfected with Mir379 inhibitor. Interestingly, Mir379 inhibitor prevented Klotho deficiency-associated H9c2 cell apoptosis. On the other hand, Mir379 mimic itself caused apoptosis in H9c2 cells. Thus, Mir379 may mediate apoptosis in H9C2 cells treated with Klotho-free medium. Using the mRNA-miRNA target interaction assay, we found that Smurf1 mRNA contained the 3-UTR binding site for Mir379. Importantly, Mir379 mimic suppressed Smurf1 expression. Therefore, Smurf1 repression may be involved in Mir379-induced H9c2 cells apoptosis.

Conclusion:
Mir379 may mediate Klotho deficiency-associated cardiomyocyte apoptosis through repression of Smurf1, which is required for Mir379-induced apoptotic cell death. Mir379 may be a potential therapeutic option for cardiomyocyte apoptosis or heart failure associated with Klotho deficiency.
Abstract P070: Differential Gene Expression In Neointima Hyperplasia In
Ucp2
Knockout Mice
Authors: Ma Shuangtao , Wang Donna
Published: September 2020

Uncoupling protein 2 (UCP2) is an inner mitochondrial membrane protein which may control mitochondria-derived reactive oxygen species. Our previous study demonstrated that knocking out the
Ucp2
gene exacerbated vascular injury-induced neointima hyperplasia while overexpressing
Ucp2
mitigated neointima formation in rodent and swine models. However, the underlying mechanism remains largely unknown. In this study, we performed transcriptome array analyses on arterial samples with and without neointima from wild-type and
Ucp2
-/-
mice to further explore UCP2-mediated regulation of neointima formation. Differential gene expression analyses (log 2-fold-change > 2 and
P
value < 0.05) identified 94 co-differentially expressed genes (co-DEGs) both between wild-type arterial samples with sham surgery and with injury-induced neointima and between arterial samples with injury-induced neointima from wild-type and
Ucp2
-/-
mice. Gene ontology analyses found that the 94 co-DEGs were mainly located in cellular components of cytoplasm and extracellular region and were enriched in biological processes including oxidation-reduction, lipid metabolic, and metabolic processes. The 94 co-DEGs were enriched in molecular functions including protein binding, protein homodimerization activity, and oxidoreductase activity. The KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis indicated that the 94 co-DEGs were mainly enriched in pathways of metabolism by cytochrome P450 and glutathione metabolism. In the protein-protein interactions (PPI) network analyses, these 94 co-DEGs formed two protein modules, and the hub genes that have a high degree of intra-module connectivity were Ppara (peroxisome proliferator activated receptor alpha), SLC2A4 (solute carrier family 2 member 4, also known as Glut4), Gpd1 (glycerol-3-phosphate dehydrogenase 1), Cxcl1 (C-X-C motif chemokine ligand 1), and Cxcl13 (C-X-C motif chemokine ligand 13). These hub genes have been shown to be mainly involved in energy metabolism and leukocyte activation. Taken together, these findings provided new insights into the molecular mechanisms underlying the protective role of UCP2 in vascular injury-induced development of neointima hyperplasia.
Abstract P084: When To Expect And Why To Analyze Cognitive Disorders In Arterial Hypertension
Authors: Krotova Viktoriia , Khomazyuk Tatyana
Published: September 2020

To study the relationship between quality of life (LQ) and cognitive impairment, as well as to identify risk factors for their development in patients with arterial hypertension (AH). Examined 509 outpatients with controlled AH stage II with SCORE risk of CVD <5 %. Non-dementia cognitive impairment were found 24,32±0,11 points on МCA scale in 164 (32.2 %). Patients also demonstrated a significant (p <0.001) decrease in the LQ indicators on all SF-36 scales compared to healthy ones by an average of 24.5-66.0 points. According to the results of correlation analysisthe most significant was the direct relationship between cognitive impairment on МCA scale and assessment of physical health (rs=+0,65; p<0,001), mental health (rs=+0,60; p<0,001), life activity limitations (rs=+0,33; p<0,001) and social activity (rs=+0,35; p<0,001), indicating an association between deterioration in LQ components and cognitive impairment.It turned out that the risk factors for developing cognitive impairment with AH were a history of cognitive impairment in close relatives (2.79 (95 % CI 1.15-6.77) compared with healthy people and 2.41 (95 % CI 1.01-5.88) - AH patients without cognitive impairment), a high vegetative index (rs +0.15; p <0.05) according to daily monitoring of BP and elevated levels of systolic BP variability in day and at night, that increased the chances of developing cognitive impairment in AH patients by 2.11 times, (rs = + 0.57 and rs = + 0.61; p<0.001). It was found that the likelihood of developing cognitive impairment exceeds 50 % (high risk) if the level of systolic BP variability is above 12 mm Hg in day (area under ROC curve AUC = 0.891; 95 % CI 0.883-0.940. (AUC = 0.891; 95 % CI 0.883-0.940; ST = 82.5 % and SP = 92.9 %) and at night – over 10 mm Hg (AUC = 0.922; 95 % CI 0.861-0.963; ST = 82.5 % and SP = 85.7 %) according to daily BP monitoring. In patients with AH for more than 10 years with dissatisfaction of life quality, even with controlled blood pressure, the presence of cognitive impairment needs to be clarified in immediate families, and pay attention to the high autonomic index and variability of systolic blood pressure monitored day and night, due to the high risk of development and progression of cognitive impairment, which worsens the prognosis of cardiovascular events.
Abstract P085: Microrna Profiling Of Vascular Smooth Muscle Cells In Human Hypertension Potential Regulators Of Endoplasmic Reticulum And Oxidative Stress
Authors: WANG YU , Camargo Livia , Beatie Wendy , McBride Martin , Montezano Augusto C , Touyz Rhian M
Published: September 2020

Numerous molecular mechanisms have been implicated in processes underlying vascular phenotypic changes and alterations in hypertension, including microRNAs (miRNAs), oxidative stress and perturbed endoplasmic reticulum (ER) function. The interplay between these elements is unclear. We assessed the VSMC miRNAs profile in hypertension focusing on oxidative and ER stress pathways. VSMCs from small arteries from normotensive (NT) and hypertensive (HT) subjects were used. miRNA profiling of 758 miRNAs was performed using TaqMan advanced miRNA assay (TaqMan Low Density Array Human microRNA). Ingenuity Pathway Analysis (IPA) was used for miRNA target prediction. Expression of vascular genes and proteins was detected by RT-PCR and immunoblotting. ROS generation (chemiluminescence) was assessed in the absence and presence of ER stress inducer tunicamycin (5μg/ml, 24h). miRNA array identified 25 miRNAs uniquely expressed in HT and 21 miRNAs uniquely expressed in NT (CT<30). Of the 332 miRNAs present in both groups, 60 miRNAs were significantly upregulated in HT (fold change >1.5), while 136 miRNAs were significantly downregulated in HT (fold change >1.5). miRNAs that were altered in hypertension, targeted genes involved in oxidative and ER stress. Pro-oxidant [Nox1 mRNA (1.71 fold), Nox4 (1.59 fold), Nox5 (2.04 fold)] and antioxidant [SOD2 mRNA (4.43 fold), GPx1 (1.97 fold)] enzymes protein levels upregulated in HT (p<0.05 vs NT). ER stress proteins, such as PERK (1.57 fold) and elF2α (2.31 fold) were also upregulated in HT (p<0.05 vs NT). IPA analysis of our miRNA library, revealed that miR-505-5p (-2.13 fold), miR-324-5p (-1.51 fold), miR-185-5p (-1.742 fold) and miR-491-5p (-1.667 fold) may regulate Nox5 levels. Moreover, miR-200b-3p (-28.57 fold) targets multiple ER stress pathways including elF2α. Treatment with tunicamycin increased ROS generation (2.29 fold) and Nox5 protein expression (1.69 fold) while downregulating SOD2 mRNA (-8.02 fold) in HT (p<0.05 vs NT). Our findings unveil the differentially expressed miRNAs and their predicted redox targets, highlighting potential interplay between VSMC ER stress, oxidative stress and miRNAs in human hypertension.
Abstract P095: Aerobic Exercise Training Reduces Endothelin-1-mediated Vasoconstriction In Postmenopausal Women
Authors: Wenner Megan M , Dow Caitlin , Greiner Jared , Stauffer Brian , Desouza Christopher
Published: September 2020

Endothelin-1 (ET-1)-mediated vasoconstrictor tone is elevated in postmenopausal women (PMW), contributing to their increased cardiovascular risk. Although aerobic exercise is beneficial in reducing ET-1 system activity in men, it is unknown whether this favorable vascular effect is conferred in women. In fact, contrary to men, it is uncertain whether aerobic exercise training improves endothelial dysfunction in PMW. We tested the hypothesis that aerobic exercise training reduces ET-1-mediated vasoconstriction in PMW. We further hypothesized reductions in ET-1 vasoconstrictor tone underly exercise-induced improvements in endothelium-dependent vasodilatation in PMW.

Methods:
Forearm blood flow (FBF) responses to intra-arterial infusion of selective ET
A
receptor blockade (BQ-123, 100 nmol/min for 60 min), acetylcholine (4.0, 8.0 and 16.0 μg/100 mL tissue/min) in the absence and presence of ET
A
receptor blockade and sodium nitroprusside (1.0, 2.0 and 4.0 μg/100 mL tissue/min) were determined before and after a 12-week aerobic exercise training intervention in 20 healthy, sedentary PMW (56
+
1 yr).

Results:
All 20 PMW completed the exercise intervention, walking an average of 4.9
+
0.1 d/wk for 50
+
2 min/d at 71
+
1% of maximal heart rate. After the exercise intervention, BQ-123 elicited no significant change in resting FBF in the previously sedentary PMW compared with significant vasodilation (~25%) before exercise. FBF responses to acetylcholine were markedly higher (~25%; P<0.05) after (from 4.3
+
0.3 to 13.8
+
0.8 mL/100 ml tissue/min) vs before (from 4.1
+
0.2 to 11.3
+
0.8 mL/100 ml tissue/min) exercise training. Moreover, before exercise training the co-infusion of BQ-123 with acetylcholine enhanced (~25%; P<0.05) the vasodilator response (from 4.3
+
0.3 to 13.7
+
0.7 mL/100 mL tissue/min) compared with acetylcholine alone; after exercise training, the presence of BQ-123 did not significantly affect the vasodilator response to acetylcholine.

Conclusions:
These data demonstrate that aerobic exercise training reduces ET-1-mediated vasoconstriction in PMW. Furthermore, decreased ET-1-mediated vasoconstriction is an important mechanism underlying aerobic exercise-induced improvement in endothelium-dependent vasodilation in PMW.
Abstract P101: Sympathetic Transduction In Young Adults With A Family History Of Hypertension
Authors: McGinty Shane J , Babcock Matthew C , Dillon Gabrielle , Matthews Evan L , Greaney Jody L , Wenner Megan M
Published: September 2020

Exaggerated sympathetic transduction (i.e., the vascular response to a burst of muscle sympathetic nerve activity; MSNA) has recently been demonstrated in certain populations of young adults at risk for future hypertension. However, it remains unknown the degree to which a family history of hypertension (FH), a risk factor for future hypertension, may influence sympathetic transduction.

Purpose:
The purpose of this study was to test the hypothesis that a +FH augments the pressor response following spontaneous bursts of MSNA at rest in young adults. A secondary purpose was to compare the influence of a +FH on sympathetic transduction between young men and women.

Methods:
We retrospectively examined beat-by-beat blood pressure (finger photoplethysmography) and MSNA (peroneal microneurography) in 21 +FH young adults (9 +FH men: 26 ± 2 yr, 25 ± 4 kg/m
2
, 12 +FH women: 22 ± 2 yr, 22 ± 3 kg/m
2
) and 15 -FH young adults (8 -FH men: 24 ± 5 yr, 25 ± 2 kg/m
2
, 7 -FH women: 22 ± 3 yr, 23 ± 3 kg/m
2
) during 10 minutes of supine rest. Signal averaging was used to characterize changes in BP for the 10 cardiac cycles following a spontaneous MSNA burst. Resting baseline variables were compared using 2-way ANOVAs. Mean arterial pressure (MAP) changes over 10 cardiac cycles following a burst of MSNA were compared using a 2-way repeated measures ANOVA (Time, FH status) and a 3-way repeated measures ANOVA (Time, FH status, Sex). Data are presented as mean ± SD.

Results:
Resting MAP (+FH: 86 ± 9 vs. -FH: 82 ± 7 mmHg;
P
= 0.14) and resting MSNA (+FH: 10 ± 6 vs. -FH: 9 ± 6 mmHg;
P
= 0.65) did not differ by FH status. The increase in MAP over the 10 cardiac cycles following a spontaneous burst of MSNA did not differ by FH status (Time,
P
< 0.0001; FH status,
P
= 0.17; Time * FH status,
P
= 0.70) and this influence did not differ between the sexes (Time * FH status,
P
= 0.58; Time * Sex,
P
= 0.06; Time * FH status * Sex,
P
= 0.99).

Conclusions:
These preliminary data suggest that spontaneous MSNA bursts do not elicit greater increases in MAP in +FH young adults, regardless of sex. Additional data are needed to determine the interactions between FH status, sex, and sympathetic transduction.

Supported by NIH Grant P20 GM 113125, P20 GM 103446, U54 GM 104941, K99/R00 HL133414, and The University of Delaware Research Foundation.
Abstract P103: Aberrant Sympathetic Neural Recruitment Strategies During Exercise Pressor Reflex Activation In Postmenopausal Women
Authors: Shoemaker Leena N , Robinson Austin T , Watso Joseph C , Greaney Jody L , Wenner Megan M
Published: September 2020

Age-related elevations in sympathetic nerve activity contribute to numerous deleterious consequences for cardiovascular health, particularly in postmenopausal women (PMW). Aging adversely affects aspects of sympathetic nervous system (SNS) coding to control blood pressure at rest and during physiological stress. Although PMW exhibit greater neural activity at rest, the underlying sympathetic discharge patterns, particularly during sympathoexcitation, remain unknown. This study aimed to test the hypothesis that PMW display aberrant neural coding strategies during physiological stress compared to young women (YW). Efferent muscle sympathetic nerve activity (microneurography) was measured at baseline and during the final minute of both 30% isometric handgrip (HG) and post-exercise ischemia (PEI) in five healthy YW (22 ± 2 y, 20 ± 4 kg/m
2
, mean blood pressure: 82 ± 7 mmHg) and five healthy PMW (60 ± 5 y, 23 ± 3 kg/m
2
, 87 ± 8 mmHg). Sympathetic action potential (AP) discharge patterns were examined using wavelet-based methodology. At baseline, PMW exhibited elevated integrated burst frequency (PMW 30 ± 10 vs YW 9 ± 3 bursts/min; p < 0.01) and increased AP firing (PMW 240 ± 117 vs YW 90 ± 64 APs/min, p = 0.04). Both groups had similar increases in integrated burst frequency during HG and PEI (p < 0.01 vs baseline). AP firing was elevated to a similar extent in both groups during HG (PMW Δ76 ± 60; YW Δ129 ± 146 APs/min; p < 0.01 vs baseline) and PEI (PMW Δ72 ± 51; YW Δ93 ± 64 APs/min; p < 0.01 vs baseline), with no change in the mean AP content per burst (p = 0.86). PMW had reduced recruitment of latent and larger AP subpopulations that were previously silent at baseline (group-by-condition interaction: p < 0.01), as evidenced by an increase in total AP clusters (binned according to peak-to-peak amplitude) during HG and PEI in YW (HG: Δ2 ± 1; PEI: Δ2 ± 2; both p ≤ 0.03 vs baseline) but not PMW (HG: Δ0 ± 1; PEI: Δ0 ± 1; both p ≥ 0.75 vs baseline). These preliminary data suggest that PMW display elevated resting sympathetic AP firing and aberrant reflex AP recruitment, such that the ability of the SNS to recruit subpopulations of previously silent axons during a sympathetic stressor is reduced in PWM compared to YW. These findings extend our knowledge of age-related neural coding strategies in women.
Abstract P106: Polysynaptic Neurotracing Of Autonomic Nuclei Projecting To Cardiovascular And Metabolic Organs
Authors: Williams Paul A , Rahmouni Kamal
Published: September 2020

Central nervous system (CNS) autonomic network plays an important role in energy homeostasis, and cardiovascular function with important pathophysiological implications. Previous studies employing pseudorabies viruses (PRV) have provided insight into the polysynaptic connections between CNS nuclei and liver, adipose tissue, or kidney. However, whether the same autonomic network is involved in the control of these three organs remain unknown. Therefore, three groups of mice received injections of PRV expressing a green fluorescent protein (GFP) into the left lobe of the liver, interscapular brown adipose tissue (iBAT), or the kidneys to compare their neuronal projections. The animals were sacrificed 5, 6, or 7 days post-injection, perfused, the brains extracted, sectioned at 50 μm thickness, stained for GFP, and imaged with confocal microscopy. Sections were matched to the mouse atlas (Franklin & Paxinos) and nuclei identified. We identified several nuclei that project to all three organs although they may represent different orders (expression appearing on different days). In the brainstem, the nucleus of the solitary tract and area postrema expressed GFP after infection of the three organs while the dorsal vagal nucleus expressed GFP after infection of the liver, but less after inoculation of the kidneys. We found GFP expression in the ventral tegmental area following liver infection and after inoculation of the kidneys or iBAT. GFP expression was noted in several hypothalamic nuclei such as the paraventricular nucleus, arcuate nucleus, lateral hypothalamus, and dorsomedial hypothalamus for all three organs. Projections from cortical and subcortical regions such as the motor cortex, bed nucleus of the striatum, septal nuclei, and preoptic nuclei were also observed from the three organs. We observed that the subfornical organ project to the liver, iBAT, and kidneys, whereas a few nuclei such as the nucleus accumbens, and insular cortex project specifically to the liver. Our study supports the existence of an overlap, but also unique, projections that sub-serve the liver, iBAT, and kidneys. The relevance of the newly identified autonomic projections to hepatic, iBAT, and renal functions is under investigation.
Abstract P119: Comparison Of Mortality Risk Of Resting Heart Rate (high Normal) With Different Levels Of Hypertension
Authors: Wen Chi Pang , Gao Wayne , chen Chien-Hua
Published: September 2020

Background and objectives:
Mortality risk of resting heart rate (RHR) has been shown to be an independent risk factor for mortality but attracted limited attention, particularly compared to hypertension. We focused on high normal RHR (80-99 beats/min), and sought equivalent risks at levels of blood pressure in hypertension.

Methods:
The cohort, 515,303 subjects free of heart disease, recruited successively from a health surveillance program between 1994 and 2008. Resting HR was determined from ECG. Deaths, 16,849, were identified from national death file as of 2011. A CVD-free sub-cohort was created by excluding those with hypertension, diabetes, smoking or high cholesterol. Life table method for life expectancy and Cox models for Hazard Ratios were calculated using RHR at 60-69/min and BP at ≦120/80 mmHg, as a common reference.

Results:
One quarter of the cohort had high normal RHR, but only 1/3 of high normal RHR had hypertension, implying a limited contribution of risks from hypertension to RHR. High normal RHR (80-99/min) as a whole had similar all-cause mortality risks (1.73), and similar number of life years shortened (6.7 years) as hypertension (≧140/90 mm Hg), but larger than JACC hypertension (≧130/80). RHR at 90-99/min had similar mortality risks (2.17) and years shortened (9.5 years) as Grade 2 hypertension (≧160/100 mmHg). In these comparisons, HR for CVD mortality, however, were slightly smaller for high normal RHR than hypertension. Other than increased CVD mortality, high normal RHR had more increases in diabetes, cancer, cirrhosis, kidney and COPD, Mortality risk of hypertension amplified by 20% when combined with high normal RHR.

Conclusion:
High normal RHR had larger risk than hypertension with BP at≧130/80, but similar as BP at ≧140/90 mmHg. RHR is as important as hypertension, in terms of all-cause mortality or in number of life years shortened. The CVD mortality risks of RHR, however, were slightly less, implying a more important role of hypertension in CVD.
Abstract P121: Metabolic Influences Of Bisphenol F Exposure In Population-based Heterogeneous Stock Rats
Authors: Clark Karen C , Holl Katie , Simonsen Derek , Velez-Bermudez Miriam , Wang Kai , Solberg Woods Leah , Lehmler Hans-Joachim , Kwtiek Anne
Published: September 2020

Bisphenol F (BPF) is marketed as a ‘safe’ substitute for bisphenol A (BPA), an endocrine disruptor associated with obesity and heart disease (i.e. cardiometabolic disease), in manufacturing polycarbonates and common consumer products. BPF’s environmental presence is growing and is detected in 66.5% of U.S. adults. Evidence of individual variation in bisphenol levels suggests that gene x environment (GxE) interactions influence cardiometabolic disease risk from bisphenol exposure. Few studies of BPF exposure in either humans or animals have been performed, thus health risks associated with BPF exposure are unknown. Traditional
in vivo
toxicity studies are performed in isogenic or genetically undefined outbred rodents, leading to conflicting results possibly due to GxE interactions. The N/NIH Heterogeneous Stock (HS) rats are a genetically heterogeneous population amenable to genetic study. Our overall study hypothesis is that BPF-induced cardiometabolic disease has underlying genetic risk, which can be identified using the HS rat model. The goal of this pilot project was to determine if BPF exposure affects growth and adiposity in HS rats. Weanling littermate pairs of male HS rats were randomly exposed to either vehicle (0.1% EtOH) or 1.125 mg BPF/L in 0.1% EtOH for five weeks in drinking water. Cardiometabolic measures, tissues, urine, and feces were taken. Our studies determined BPF exposure in HS rats significantly increases body growth (154.2 ± 3.0 g vs 160.9 ± 3.2 g, p=0.03). BPF exposure alters body composition seen in nuclear magnetic resonance measurements by increasing %fat (7.8 ± 0.3 % vs 8.4 ± 0.3 %; p=0.06), mirroring the significant increase in gonadal white adipose tissue (GWAT) mass (7.58 ± 0.29 mg/g vs 8.37 ± 0.34 mg/g, p=0.01) and perirenal white adipose tissue mass (10.6 ± 0.5 mg/g vs 12.2 ± 0.5 mg/g, p<0.01) in BPF-exposed males. Linear regressions of liver
Ugt1a9
expression, an enzyme implicated in BPF metabolism, and %fat or GWAT mass were significantly different between exposure groups (%fat p=0.02, GWAT p=0.02), suggesting that
Ugt1a9
expression is related to adiposity phenotype development in BPF-exposed rats. Our data suggest that BPF exposure increases body growth and adiposity, which are risk factors for cardiometabolic disease.
Abstract P132: A Kidney-Targeted Nanoparticle To Augment Renal Lymphatic Density Decreases Blood Pressure In Mice With L-NAME- And Angiotensin II-Induced Hypertension
Authors: Goodlett Bethany L , Yoo Eunsoo , Kang Chang Sun , Balasubbramanian Dakshnapriya , Love Sydney , Tate Winter , Chavez Delilah , Nabity Mary , Kim Dongin , Rutkowski Joseph M , Mitchell Brett M
Published: September 2020

Chronic interstitial inflammation and renal infiltration of activated immune cells play an integral role in hypertension. Lymphatic vessels attenuate inflammation by trafficking activated immune cells and excess fluid from the interstitial space to lymph nodes. Previously, our laboratory demonstrated that genetically inducing renal lymphangiogenesis could treat hypertension in three different mouse models. In an effort to translate these findings into a clinical treatment, we hypothesized that a targeted nanoparticle could deliver the pro-lymphangiogenic factor VEGF-C156S to the kidney, induce lymphangiogenesis, and lower blood pressure in hypertensive mice. A micellar nanoparticle was developed with the capacity to deliver protein to the kidney, as demonstrated through delivery trials. This nanoparticle was loaded with VEGF-C156S and injected into mice with LNAME-induced hypertension (LHTN) or angiotensin II-induced hypertension (AIIHTN) via tail vein every 3 days. Compared to hypertensive mice injected with VEGF-C156S only (no nanoparticle) every 3 days, nanoparticle-treated mice exhibited a significantly lower systolic blood pressure (SBP) after 4 injections (LHTN SBP: 160±5 vs. 120±3 mmHg, p<0.001; AIIHTN SBP: 150±8 vs. 126±6 mmHg, p=0.03). Immunolabeled kidney sections from nanoparticle-treated LHTN mice showed a significant increase in podoplanin+ pixels, corresponding to an increase in lymphatic vessel density (p<0.01). A 5-fold increase in renal gene expression of podoplanin in nanoparticle-treated LHTN mice further supported this finding (p=0.01). Flow cytometric analysis of the nanoparticle-treated LHTN mice showed decreased renal CD45+F4/80+CD11c- cells, while AIIHTN mice revealed decreased levels of renal CD45+CD3e+, CD45+CD4+CD8-, and CD45+F4/80+CD11c+ cells (p<0.01, p=0.03, and p<0.001, respectively) when compared to their respective hypertensive groups. These data support our previous findings that expanding the renal lymphatic vasculature can treat existing hypertension by reducing renal immune cells. The results of this study may provide clinicians with a renal lymphatic-targeted therapeutic for treating hypertensive patients.
Abstract P158: Addressing Hypertension And Aging In Growing Pakistani Elderly San Joaquin Population
Authors: Siddiqui Maha
Published: September 2020

Introduction:
San Joaquin Pakistani elderly population (SJPEP) face health problems due to poor nutritional habits, financial and emotional stress from loss of social status, loss of physical capabilities, loneliness, reduced income which can increase risk for hypertension and cardiovascular disease (CVD). Pakistan is ranked as the 12th highest source country for immigration into the United States. SJ has a growing rate of at risk for hypertension elderly Pakistani immigrants who live with their full time working adult children.

Objectives:
Trainees conducted hypertension screenings at mosques located in the most medically served county, San Joaquin (SJ) to reduce the risk of CVD and spread awareness on hypertension, stress management, nutrition, exercise, and their implications in the Pakistani population.

Methods:
I trained medically ambitious low-income minority high school students to conduct blood pressure screenings and serve as a health technology coach for the Pakistani elderly population at mosques. Hypertension screenings, stress management guidance, nutrition, and heart health talks were conducted at SJ mosques with Imam (religious leader) for adult children and the elderly.

Findings:

-About 86% (128 of 149) of SJPEP felt financial and emotional stress in the last year

-About 48% (71 of 149) of SJPEP are hypertensive

-About 48% (71 of 149) of SJPEP are at risk for CVD

-About 2% (3 of 149) of SJPEP reported daily physical exercise

-About 22% (33 of 149) of SJPEP were encouraged to physically exercise

-About 95% (141 of 149) of SJPEP eat more than 4 servings of red meat per week

-About 94% (140 of 149) of SJPEP prefer rest over physical exercise

-About 75% (111 of 149) of SJPEP felt dissatisfied by San Joaquin medical treatment

Direct Outcomes:

-Development of self-advocacy for health in the Pakistani elderly community

-Improved patient-provider trust

-Youth learned the value of empathy, multiculturalism, and service to disadvantaged communities through the program and volunteering

-Adult children felt more confident in taking care of their elderly parents with nutrition and physical therapy

-Program students are determined to pursue medicine and address community concerns in low-income minority groups and diversity of cultures
Abstract P170: Validation Of A Practical Approach To Blood Pressure Measurement: Secondary Analysis Of Data From A Nationally Representative Household Survey In India
Authors: Shivashankar Roopa , Sharma Bhawna , Moran Andrew E , Pathni Anupam K
Published: September 2020

Background:
Various clinical guidelines differ on the required number of blood pressure (BP) measurements during clinic visits. The research standard approach is measuring BP three times and using the mean of the last two readings. India’s National Programme for Prevention and Control of Cancer, Diabetes, Cardiovascular Diseases and Stroke (NPCDCS) recommends measuring twice and averaging the two readings. We hypothesized that a selective, practical approach to BP measurement in public health settings would be simpler, avoid calculating the mean, but not substantially erode measurement accuracy.

Method:
We used the data of adults (aged 30-54 years) from the National Family Health Survey (2015-16), with three seated BP measurements for each participant (N= 372,110). In the practical BP measurement approach, if the first reading is <140/90 mm Hg, the first BP was used. If first BP is ≥140/90 mm Hg, the second BP was used. If the difference between the two systolic or diastolic BP readings was ≥5 mm Hg, then third BP was used. We compared the accuracy of practical and NPCDCS approaches in stratifying high BP (≥140/90 mm Hg), each referencing against research standard.

Results:
The prevalence of high BP was 15.5% (95% CI: 15.5%, 15.7%), 14.9% (14.9%, 15.1%), and 19.3% (19.3%,19.5%), when used the standard, practical, and NPCDCS approaches, respectively. Referencing the research standard, the sensitivity, specificity, false positive and false negative rates of the practical approach were 85.4%, 98.0%, 11.3% and 2.7%; rates of the NPCDCS approach were 94.3%, 93.4%, 25.1% and 1.3%, respectively. For categorizing the stages of high BP, the agreement and kappa statistics for practical vs. standard were 94.7% and 0.80 at p <0.0001 and NPCDCS vs. standard were 92% and 0.742 at p <0.0001. The mean number of BP measurements required per person was 1.4 for the practical approach compared with 2.0 for the NPCDCS approach.

Conclusions:
Both the practical and NPCDCS approaches to BP measurement had high validity and agreement with the research standard. The practical approach is simpler and involves a lower measurement burden on health care professionals; this approach could improve the utility of BP measurement and hypertension diagnosis in public health settings.
Abstract P181: Musical Improvisation In Labile Hypertension
Authors: Corbett Jeffrey , Nickels Mark W , Azzara Christopher D , Bisognano John D
Published: September 2020

Background:
Patients with labile hypertension experience transient but substantial increases in blood pressure, usually surrounding episodes of emotional distress and anxiety. Inability to express negative emotions may also play a substantial role. Most psychological interventions are aimed at blunting the stress response to anxiety or distress (i.e. mindfulness techniques). We hypothesize that musical improvisation therapy may blunt emotional response but may also decrease brain activity associated with negative thinking and emotions.

Materials/methods:
We surveyed 20 individuals with labile hypertension. Subjects completed a pre- and post-intervention and also had their blood pressure checked pre- and post-intervention. The intervention involved subjects actively engaging in a roughly one hour-long interactive musical improvisation simulation delivered via electronic media.

Results:
Nine out of 20 participants had a positive responsive to the exercise (SBP drop
>
10mmHg). Fifty-eight percent of all subjects and 63% of positive responders felt the exercise made them feel less self-conscious and self-critical. Sixty-seven percent of all subjects who endorsed struggling with mindfulness felt that this exercise would help them practice mindfulness more regularly.

Discussion:
One of the most difficult judgments to make is whether a patient’s office hypertension is due to isolated “white coat spike” or whether the elevated readings represent a potentially physically damaging recurring hyperadrenergic response to life stressors. Most efforts of combating labile hypertension, such as yoga and relaxation techniques, aim at blunting the stress response, but results are variable. Yet, labile hypertension may well additionally be linked to inhibition of the expression of negative emotions. The neural complexes involved in musical improvisation appear to not only increase pleasure but also decrease activity in brain structures associated with negative thoughts and emotions.

Conclusion:
Our data supports the conclusion that musical improvising has the potential to both blunt emotional distress (i.e. through mindfulness) and decrease negative thoughts and emotions. Both pathways can potentially lessen the impact of labile hypertension.
Abstract P182: Workforce Reforms And Task Sharing To Improve Hypertension Treatment Coverage In India
Authors: Marklund Matti , Cherukupalli Rajeev , Pathak Priya , Neupane Dinesh , Krishna Ashish , Wu Jason H , Moran Andrew , Matsushita Kunihiro , Appel Lawrence J
Published: September 2020

Background:
Most patients with hypertension in India are not treated, in part due to insufficient healthcare providers.

Objective:
Estimate the current hypertension treatment capacity of the public healthcare system in India and simulate the effects of workforce system and treatment reforms designed to increase coverage of hypertension treatment.

Methods:
We estimated the hypertension treatment capacity and salary costs of public healthcare facilities (subcenters, primary and community healthcare centers) under different assumptions on workforce size, task sharing, and treatment frequencies.

Results:
In 2020, an estimated 9% of all hypertensives in India (~23 million adults) are being treated for hypertension in subcenters and primary/community healthcare centers. Treating 30% of hypertensives without task sharing would require an additional >400,000 staff and >340 billion INR/year in salaries (
Figure
). Task sharing under current legislation was estimated to allow the current workforce to treat 14%, while a feasible extension of task sharing beyond the current legislation (e.g., allowing nurses to prescribe medicines) could treat 57% of hypertensive adults with the same workforce. Applying quarterly visits in addition to the extended task sharing, the current workforce could treat all hypertensives adults in India.

Conclusion:
Under the current practice, even modest increases of hypertension treatment coverage will require substantial additional human and financial resources. Extended task sharing plus fewer visits with longer prescription period may achieve nationwide hypertension treatment at public systems without additional workforce.
Abstract P188: Building A Pipeline To Address San Joaquin Health Inequity
Authors: Siddiqui Maha
Published: September 2020

Introduction:
San Joaquin Valley (SJV) is the most underserved valley for health care with the lowest ratios of physicians for any region in California. For the last 40 years, SJV continues to face health inequity and disparities with not enough physicians to tend to the community. With a diverse community of low income and minority groups, the lack of physicians do not represent the workforce of SJV. Many of the talented youth who aspire to be physicians from SJV leave to bigger cities rather than coming back to enrich their vulnerable communities.

Objectives:
I created no cost pipeline medical programs (summer program, year long internships and online class) for SJV high school students to increase diversity in the medical profession, encourage underrepresented in medicine (URM) students to pursue medicine and come back to SJV to practice medicine in an effort to lower the patient provider gap.

Methods:
I trained and provided mentorship to medically ambitious low-income high school students in the programs to better understand SJV health inequity to instill a passion in them to come back after their medical education to practice medicine in SJV. Through the program, students learned about SJV health disparities and applied precision medicine to their own health inequity projects in SJV.

Findings:

-About 46% (33 of 72) of program participants were first generation

-About 47% (34 of 72) of program participants identified as URM

-About 65% (47 of 72) of program participants aspire to practice medicine in SJV

-About 83% (60 of 72) of program participants feel that the pipeline program has helped them solidify their passion in medicine

-About 100% (72 of 72) of program participants feel the program gave them guidance in health disparities, precision medicine, and applying design thinking concepts as a future leader in medicine

Direct Outcomes:

-Students were able to understanding community concerns beyond science and apply community activism through a precision medicine lens

-Served as agents of change by directly communicating with physicians and understanding the need for more URM physicians

-Students received mentorship and confidence to rise as first generation college students

-Youth learned the value of service to disadvantaged communities
Abstract P206: Prenatal Cadmium Burden, Birth Weight, And Offspring Adolescent Blood Pressure
Authors: Suter Megan K , Enquobahrie Daniel , Karr Catherine , Sathyanarayana Sheela , Flynn Joseph T , Lamadrid-Figueroa Hector , Hernandez-Avilla Mauricio , Peterson Karen , Hu Howard , Tellez-Rojo Martha M
Published: September 2020

Background:
Cadmium is a ubiquitous, toxic heavy metal associated with several adverse health outcomes, including high blood pressure, in adults. The impact of maternal cadmium burden on offspring birth weight and have not been thoroughly explored. We investigated associations of prenatal cadmium burden with birth weight and offspring blood pressure in childhood and adolescence.

Methods:
We analyzed data from 202 mother-child pairs who were recruited for the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) study in Mexico City (1997-2000). Prenatal cadmium burden was characterized using maternal urine collected in the third trimester of pregnancy - continuous and quartile specific-gravity adjusted cadmium (log-UCd, μg/L). Outcomes were offspring birth weight and blood pressure (measured at age 7-15 years). Blood pressure status (normal, elevated, stage 1 hypertension) was defined based on the 2017 American Academy of Pediatrics Guidelines. Those with elevated or stage 1 hypertension were categorized as having high blood pressure. Linear and logistic regression models were used to examine associations, adjusted for potential confounders. Potential effect modification by offspring sex was assessed using interaction terms and sex-stratified models.

Results:
Study participants included 93 males and 109 females, with a mean age of 10.0 (SD=1.5) years. Median third trimester urinary cadmium concentration was 0.17 μg/L (IQR=0.12, 0.26). The prevalence of high blood pressure was 19.3% (39/202). Prenatal cadmium was not associated with birthweight (β=-58.94 grams, 95%CI: -138.07, 20.19), offspring systolic blood pressure (β=-0.90 mmHg, 95%CI: -2.87, 1.06), diastolic blood pressure (β=-1.21 mmHg, 95%CI: -2.68, 0.26), or high blood pressure (OR=0.64, 95%CI: 0.34, 1.21). We found similar results when prenatal cadmium was modeled with quartiles. There was no evidence of effect modification by sex for any of the outcomes.

Conclusions:
In the current study, maternal third trimester was not associated with offspring blood pressure or birth weight, however future studies are needed to confirm these findings.
Abstract P211: B Cells Contribute To Hypertension And Cytolytic Nk Cell Activation In Response To Placental Ischemia In Pregnancy
Authors: Herrock Owen , Amaral Lorena M , Fitzgerald Sarah , Lemon James , Deer Evangeline M , Ibrahim Tarek , Campbell Nathan , Usry Nathan , Lamarca Babbette B
Published: September 2020

Preeclampsia (PE), new onset hypertension during pregnancy, is associated with inflammation and B cells secreting agonistic autoantibodies against the angiotensin II type 1 receptor (AT1-AA). Two recognized subsets of B Cells are B1 and B2 B Cells. B2 B Cells are involved in adaptive immune responses and produce specific antibodies. B1 B Cells produce natural antibodies and are implicated in the pathophysiology of PE through AT1-AA. The Reduced Uterine Perfusion Pressure (RUPP) rat model of placental ischemia recapitulates many characteristics of PE. We have previously shown that either B cell depletion or AT1-AA epitope binding protein (7AA) in RUPP rats improved hypertension. It is currently unknown which B cell subsets make the AT1AA in PE. This information would add to the design of new therapies targeting one B cell type for depletion. Therefore, we hypothesize that B cells and specifically B2 cells cause hypertension and NK cell activation during pregnancy through production of the AT1-AA. To test this hypothesis, total splenic B Cells and B2 cells were isolated from RUPP rats on Gestation Day (GD)19 RUPP and adoptively transferred into NP rats on GD12, blood pressure (MAP), placental and circulating cNKs were measured by flow cytometry on GD19. To test the role of AT1-AA in the hypertension, 7AA was administered to a group of recipient rats on GD14. MAP increased in NP+RUPP B cells to 116 ± 3 mmHg, n=11, and to 112 mmHg ± 2, n=12, in NP+RUPP B2 cells, compared to NP rats(p<0.001). Administration of 7AA attenuated hypertension in response to total RUPP B cells (99 mmHg ± 6, n=5)(p<0.01) and in response to RUPP B2s (98 mmHg ± 4, n=6) (p<0.05). Circulating cNKs were elevated in NP+RUPPBcells (6 ± 2.5, n=5)(p<0.01) and in NP+RUPP B2 cells (4.8 ± 1.6, n=11)(p<0.01) compared to NP (0.275 ± 0.2, n=11). Placental cNKs were elevated in NP+RUPPBcells (2.32 ± 0.73, n=6)(p<0.01) and in NP+RUPP B2 cells (1.01 ± 0.2, n=11)(p<0.01) compared to NP (0.225 ± 0.2, n=11). In conclusion total B Cells and B2 B cells activated in response to placental ischemia cause hypertension via secretion of the AT1-AA and NK cell activation during pregnancy and play an important role in PE.
Abstract P212: Kidney Injury Caused By Preeclamptic Pregnancy Improves Postpartum In A Transgenic Rat Model
Authors: Kedziora Sarah M , Kraeker Kristin , Markó Lajos , Mueller Dominik N , Dechend Ralf , Haase Nadine , Herse Florian
Published: September 2020

Preeclamptic pregnancies involve mild renal injuries. However, there has been evidence that women with a history of preeclampsia (PE) have an increased risk to develop kidney disease in association to high blood pressure later in life. This study aims to characterize renal injury during pregnancy and postpartum in an established transgenic rat model for PE. Female Sprague-Dawley rats transgenic for the human angiotensinogen gene develop a PE phenotype in pregnancy, including cardiac remodeling, when mated with male rats harboring the human renin gene. Postpartum, blood pressure restores but cardiac remodeling persists. We hypothesize that PE during pregnancy mediates kidney injuries but does not fully restore after ending of the high blood pressure (postpartum). The renal alterations were analyzed by histological staining, gene expression and urine analysis. PE rats have elevated mean arterial blood pressure during pregnancy (PE
d19
148.4 ± 20.7 mmHg) compared to normotensive values in control animals (WT
d19
105.3 ± 4.6 mmHg). During PE increased expression of
kidney injury marker 1
(
Kim-1/18S
: PE
d21
4.14 ± 3.26; WT
d21
0.08 ± 0.02),
neutrophil gelatinase associated lipocalin 2
(
Ngal/18S
: PE
d21
1.64 ± 0.83; WT
d21
0.59 ± 0.28) and
connective-tissue growth factor
(
Ctgf/18S:
PE
d21
1.51 ± 0.46; WT
d21
0.92 ± 0.32) were detected. Kidneys of PE rats showed mild glomerular (PAS-positive glomerular area PE
d21
86.2 ± 4.4%; WT
d21
79.1 ± 3.2%) and tubular changes during PE pregnancy resulting in albuminuria (albumin/creatinine ratio PE
d19
2193.8 ± 1878.2; WT
d19
290.4 ± 252.0). However, 4 weeks after pregnancy (approx. 2 years in humans) most of the PE related renal damages were absent including albuminuria and elevated expression of biomarkers (
Kim-1/18S
: PE
d50
0.09 ± 0.05; WT
d50
0.23 ± 0.13;
Ctgf/18S
: PE
d50
0.78 ± 0.25; WT
d50
0.8 ± 0.25;
Ngal/18S
: PE
d50
0.37 ± 0.17; WT
50
0.47 ± 0.11). Only mild enlargement of glomerular tuft area (PE
d50
7523.8

± 418.7 μm
2
; WT
d50
7058.4 ± 198.8 μm
2
) was detected. Overall, the glomerular and tubular injuries are present during pregnancy in this transgenic PE rat. Most restore postpartum, speculating long-term kidney failure observed in humans is associated to hypertension and additional cardiovascular events.