bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P018: The Angiotensin Type 2 Receptor (AT
2
R) Is Involved In The Etiology Of Inverse Salt Sensitivity Of Blood Pressure
Authors: Xu Peng , Sarpong Kwabena , Gildea John J , Marshall Stephen , Yue Wei , Schiermeyer Katherine , Felder Robin
Published: September 2020

Renal proximal tubule (RPT) dopamine D
1
-like receptors (D
1
R) and angiotensin II type-2 receptor (AT
2
R) inhibit sodium reabsorption and counter regulate the renin angiotensin systems AT
1
R which stimulates sodium reabsorption. Salt sensitivity of blood pressure (SS) is defined as a ≥7-mmHg rise in blood pressure following a week of daily consumption of 350 mM sodium chloride (NaCl). Inverse salt sensitivity (ISS) is defined as a ≥7-mm Hg increase in blood pressure (BP) after a week of 10 mM NaCl/day. Salt resistant controls were defined as < 7mM Hg change in BP whether on 10 or 350mmHg NaCl/day for one week. Previously, we demonstrated that D
1
R RPT membrane recruitment was inversely proportional to an individual’s degree of BP increase on a 350 mM diet. We hypothesize that the degree of salt sensitivity of blood pressure would be inversely correlated with the recruitment of the AT
2
R to the plasma membrane induced by NaCl. Immunostaining shows that D
1
R was distributed in a fine granular manner throughout the whole plasma membrane, while AT
2
R shows a punctate pattern in both urine-derived SR and ISS RPTCs. There was no difference of basal D
1
R or AT
2
R expression. Increasing cell NaCl (monensin ionophore 10 μM, 1 hour) resulted in a significantly more AT
2
R and D
1
R(control) recruitment to cell surface in ISS cells than in SR cells (D
1
R: MON/VEH: SR, 1.032 ± 0.056, n=4; ISS, 1.537 ± 0.097, n=4; t-test, p<0.01; AT
2
R :MON/VEH: SR, 0.923 ± 0.063, n=3; ISS, 1.28 ± 0.106, n=3; t-test, p<0.05). Because ISS individuals present to the medical system with elevated blood pressure while on a low salt diet, they are often misdiagnosed as hypertensive. As our studies were conducted on RPT cells isolated from individual's urine, the D
1
R and AT
2
R response may contribute to the diagnosis of ISS individuals with elevated blood pressure while on a 10 mM salt diet, and provide better understanding on the etiology of ISS.
Abstract P043: Correlation Between Blood Pressure And Left Ventricular Metabolism In HIV Individuals With And Without Cocaine Use As Assessed By FDG-PET/CT
Authors: Bhattaru Abhijit , Ghorpade Rina , Rojulpote Chaitanya , Bravo Paco E , Patil Shivaraj , Gonuguntla Karthik , Karambelkar Pranav , Vuthaluru Kiranmayi , Zhang Vincent , Werner Thomas J , Alavi Abass
Published: September 2020

Objectives:
Elevated blood pressure from cocaine can increase left ventricular (LV) metabolic activity, leading to structural changes such as hypertrophy. We aimed to assess the association between blood pressure and LV myocardial uptake of FDG, hypothesizing that HIV individuals with raised blood pressure will have higher FDG uptake.

Methods:
University of Pennsylvania enrolled patients with HIV on antiretroviral therapy with viral load <200 copy/ml. Cocaine usage in moderate to high amounts (cocaine disease score≥5) was subsequently documented. Full body PET scans were acquired 120 minutes post-injection of 18F-FDG(15 mCi) with low-dose CT scans for attenuation correction. Patients with imaging artifacts were excluded from the analysis. Regions of interest were drawn on axial slices using computer software (OsirixMD, v9.0.02) around LV myocardium. Average standard uptake value means (aSUVmean) were calculated for each patient. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were obtained prior to imaging; mean arterial pressure (MAP) was subsequently calculated. Linear regressions and Mann-Whitney U tests were employed for statistical analysis.

Results:
aSUVmean was higher in HIV patients with cocaine use (U(Ncocaine = 11, Nno cocaine=11) = 93, p=0.0336). In patients with cocaine use, there was a positive correlation between blood pressure and aSUVmean (SBP: r=0.70, p=0.0164; DBP: r=0.69, p=0.0185; MAP: r=0.72, p=0.0120). No significant correlations were found in HIV patients without cocaine use (SBP: r=0.03, p=0.9239; DBP: r=-0.50, p=0.1153; MAP: r=-0.32, p=0.3345).

Conclusions:
LV myocardial metabolism was more strongly positively correlated with blood pressure in HIV patients using cocaine compared to HIV patients without cocaine. These data suggest FDG-PET/CT can be used to monitor LV metabolic activity and allow for timely assessment of structural changes caused by cocaine use and hypertension.
Abstract P045: Sex And Age Specific Circulating Aldosterone Changes In Transgenic Hypertensive (mRen2)27 Rats And Hannover Sprague Dawley (SD) Rats And Its Association With Blood Pressure And Cardiac Function
Authors: Ryalat Fatima , Cruz-Diaz N , Graham W , Gwathmey-Williams T , Gallagher P E , Tallant E A , Yamaleyeva L M , Diz D I
Published: September 2020

Aldosterone plays a significant role in hypertension and target organ damage. Aldosterone antagonists are used in the management of heart failure. However, neither the influence of age nor sex on aldosterone pathophysiology is well understood. We investigated the changes in circulating aldosterone with age and its association with cardiovascular function, using male and female hypertensive renin transgenic (mRen2)27 rats and SD rats at 20 and 50 weeks of age. Both male (22 ± 3 vs. 12 ± 2 ng/dL, n = 9 - 12, p < 0.05) and female (59 ± 10 vs. 23 ± 8 ng/dL, n = 6 - 10, p < 0.05) hypertensive rats had higher serum aldosterone compared with SD rats at 20 weeks of age. At 50 weeks of age, the difference persisted in the hypertensive female rats (63 ± 8 vs. SD: 33 ± 7 ng/dL, n = 6 - 7, p < 0.05), but not in the males. SD male rats have higher systolic blood pressure (SBP) as they age, and consequently develop cardiac diastolic dysfunction associated with higher aldosterone at 50 weeks compared to 20 weeks (28 ± 3 vs. 12 ± 2 ng/dL, n = 7 - 9, p < 0.05). This aging effect on aldosterone was not significant in the other groups. We showed previously that SD males treated with polyphenol rich muscadine grape extract (MGE) have lower aldosterone, less aortic stiffness and better cardiac diastolic function (E/e’) than controls at the older age; the MGE effect was not seen in (mRen2)27 males. Sex differences in aldosterone were not significant in the SD rats at either time point. However, (mRen2)27 female rats had higher aldosterone than (mRen2)27 males at both 20 weeks (59 ± 10 vs. 22 ± 3 ng/dL, n = 10 - 12, p < 0.05) and 50 weeks (63 ± 8 vs. 31 ± 7 ng/dL, n = 6 - 7, p < 0.05), despite the lack of significant differences in SBP. (mRen2)27 female rats preserve cardiac function better than males throughout their life span, while males develop indices of heart failure. Our data suggest that lower aldosterone levels in hypertensive males compared with females do not protect against the higher lifetime burden of elevated SBP and also may reflect different mechanisms controlling circulating aldosterone between sexes. In addition, data suggest a potential therapeutic effect of MGE in the management of age-associated moderate hypertension.
Abstract P054: The Benefits Of Physical Activity On Cardiovascular Indicators In Community-dwelling Hypertensive Older Adults: A Nationwide Health Examination Cohort Data In Korea
Authors: Ahn Jeong-Ah
Published: September 2020

Purpose:
The aim of this study was to explore the effects of physical activity on cardiovascular indicators in community-dwelling hypertensive older adults.

Methods:
This study was a longitudinal study using the Elderly Cohort Database of National Health Insurance Service in Korea between 2002 and 2013. Participants were 10,588 older adults with hypertension. The author extracted variables of physical activity, blood pressure, blood glucose, body mass index, and total cholesterol levels for 11 years from the database. Participants were divided into 4 groups according to the changes in physical activity performance over time in 2013; Group I (totally inactive), II (inactive to active), III (active to inactive), and IV (totally active). Cox proportional hazard model was used to confirm the risk of cardiovascular indicators over time in each group.

Results:
Participants’ mean age was 64.2 years in the initial year of 2002. The number of participants in Groups I, II, III, and IV was 4032, 2697, 1919, and 1940, respectively. As a result, Group IV had a significantly decreased risk for uncontrolled hypertension by 13% compared to Group I (HR = 0.87, 95% CI = 0.800-0.948). Also, Group II showed a significantly decreased risk for uncontrolled diabetes by 6% compared to Group I (HR = 0.94, 95% CI = 0.888-0.999).

Conclusion:
Physical activity is one of the most important non-pharmacological and self-management intervention that can be easily applied to older adults with hypertension. It is considered that the continuous performance of physical activity can significantly lower the long-term cardiometabolic risks in older adults. Healthcare providers should be aware of the importance of the physical activity of older adults and encourage them to perform and maintain it steadily for better long-term cardiometabolic outcomes.
Abstract P057: Arterial Stiffness And Pressure Wave Reflection In The Development Of Isolated Diastolic Hypertension
Authors: Tomiyama Hirofumi , Shiina Kazuki N , Chikamori Taishiro , Yamashina Akira
Published: September 2020

Importance:
While increased arterial stiffness and augmented pressure wave reflection are thought to be key factors in the development of systolic/diastolic hypertension (SDHT) or isolated systolic hypertension (ISHT) via the elevation of systolic blood pressure, their associations with the development of isolated diastolic hypertension (IDHT) have not been clarified.

Objective:
To examine the significance of augmented pressure wave reflection in the absence of accompanying increase of the arterial stiffness in the development of IDHT.

Design and Setting:
The prospective observational study conducted in the employees of a Japanese construction company at its health care center from year 2007 through year 2015 with a mean follow-up of 6.4 years, respectively.

Participants:
A total of 3022 Japanese male employees without hypertension at the start of this study.

Main Outcomes and Measures:
The annual assessment of prevalence of any phenotypes of hypertension. The blood pressure, brachial-ankle pulse wave velocity (baPWV), and radial augmentation index (rAI) were measured annually during the study period.

Results:
At the end of the study period, 129 subjects were diagnosed as having SDHT, 112 as having ISHT, and 74 as having IDHT. Both the baPWV and rAI showed significant individual odds ratios for new onset of SDHT and new onset of ISHT. However, only rAI, but not the brachial-ankle PWV, showed a significant odds ratio (1.44, P<0.01) for new onset of IDHT. This association was significant in subjects without elevated baPWV values at the start of the study (i.e., baPWV
<
1224 cm/sec), but not in those with elevated brachial-ankle PWV at the start of the study. Generalized estimating equation analyses demonstrated a significant longitudinal association of the rAI, but not baPWV, with the prevalence of IDHT (estimate = 0.02, P=0.02).

Conclusions:
While increased arterial stiffness and augmented pressure wave reflection present concomitantly may be associated with the development of SDHT and ISHT, augmented pressure wave reflection alone, which may be related to isolated peripheral vascular damage, in the absence of accompanying increase of the arterial stiffness, may be a significant factor in the development of IDHT.
Abstract P067: Piezo1 Activation Inhibits Adipogenesis And Lipogenesis In Perivascular Adipose Tissue Preadipocytes
Authors: Rendon Mora Cristian Javier , Flood Emma D , Watts Stephanie W , Contreras G.Andres , Thompson Janice
Published: September 2020

In adipogenesis, perivascular adipose tissue (PVAT) preadipocytes turn into adipocytes. In non-PVAT preadipocytes, mechanical forces affect the commitment and lipogenic stages of adipogenesis. The mechanism may involve PIEZO1, a mechanosensor, that boosts differentiation of progenitor cells towards osteogenic and fibroblastic lineages. Since hypertension causes changes in the vascular forces that could affect adipogenesis in PVAT, our objective was to evaluate PIEZO1 expression patterns in PVAT and the effects of PIEZO1 activation on the adipogenic potential of preadipocytes. We hypothesize that PIEZO1 activation limits the adipogenic potential of PVAT preadipocytes. PVAT from the thoracic aorta (APVAT) was collected from male Sprague Dawley rats at 10 weeks of age (n=5). Preadipocytes were obtained by Liberase digestion followed by serial passage of adherent cells. Preadipocyte progenitors, CD34+PDGFRα+, were harvested by magnetic-activated sorting. PIEZO1 expression was assessed by RT-qPCR and immunofluorescence (IF). Preadipocytes were induced to differentiate for 14 d in standard media (CON) or in the presence of PIEZO1 agonist Yoda (10μM) and inhibitor Dooku (5μM) during days 0-2 (commitment), 3-14 (lipogenesis), and 0-14 (overall adipogenesis). Adipogenesis was evaluated with IncuCyte Live-Cell system using the triglyceride stain Bodipy 493503. Triglyceride content is reported as Bodipy Intensity/Adipocyte Count. Piezo1 RNA was expressed in adipocytes and the stromal vascular fraction of APVAT. PIEZO1 IF signal was detected in SVF and preadipocyte. Triglyceride was reduced by Yoda (62 ± 14.3) and Dooku (49.3 ± 14) during 0-2 d compared to CON (312.5 ± 165.6). Neither Yoda nor Dooku for 12 d affected triglyceride accumulation compared to CON. In contrast, the lipid content of Yoda (77.7 ± 21.3) and Dooku (48.9 ± 15.2) treated cells during 14 d was reduced vs CON (312.5 ± 165.6). The expression of PIEZO1 in all PVAT fractions suggests mechanosensitivity. PIEZO1 activation during adipogenesis commitment impaired adipocyte maturation. These data provide evidence for the capacity of mechanosensory expressed in PVAT preadipocytes to modulate adipogenesis, underpinning the deleterious impact of hypertension on PVAT function.
Abstract P076: Cerebral Vascular Dysfunction Precedes Cognitive Impairment In Alzheimer’S Disease
Authors: Fang Xing , Zhang Huawei , Wang Shaoxun , Liu Yedan , Gao Wenjun , Roman Richard J , Fan Fan
Published: September 2020

Alzheimer’s disease (AD) is the most common form of dementia and is a major financial burden to the health care system. The prevailing view is that cholinergic deficiency, amyloid-beta (Aβ) accumulation, and Tau protein abnormalities are the primary underlying causes of neurodegeneration in AD, but unsuccessful clinical trials targeting these pathways have led the community to reconsider alternatives such as the vascular hypothesis. However, it is still uncertain whether cerebral vascular impairment is a cause or consequence of dementia in AD. Previous studies have demonstrated that a TgF344-AD model expressing mutant human amyloid precursor protein (
APP
) and presenilin 1 (
PS1
) genes exhibits Aβ accumulation and cognition deficiency at 24 weeks of age. In the present study, we compared the myogenic response (MR) of the middle cerebral artery (MCA) and parenchymal arteriole (PA) in 8-, 16- and 24-week TgF344-AD and WT F344 rats. We first confirmed that TgF344-AD rats exhibited learning and memory dysfunction at 24-week of age, and they took 2-time longer to escape than WT rats using an eight-arm water maze. There was no difference in the MR of MCA and PA at 8 weeks of age in AD and WT rats. However, AD rats exhibited an impaired MR at 16-week of age as the inner diameter of the MCA of AD rats only decreased by 6.6 ± 1.7% vs. 10.7% ± 1.0% in WT rats when perfusion pressure was increased from 40 to 180 mmHg. The impaired MR was exacerbated in AD rats at 24-week of age. These findings suggest that impaired MR of cerebral vasculature precedes the development of a cognitive deficiency. Since the MR protects the cerebral microcirculation from elevations in pressure, an impaired MR and cerebral blood flow autoregulation could result in blood-brain barrier leakage that contributes to neurodegeneration and cognitive impairment. Our results provide novel insight in understanding the pathogenesis of AD, which will lay the foundation for the discovery of new biomarkers in AD.
Abstract P079: Lymphatic Contraction Was Enhanced In Spontaneously Hypertensive Rats
Authors: Mukohda Masashi , Matsui Toshiyasu , Ozaki Hiroshi , Mizuno Risuke
Published: September 2020

Because lymph capillary network regulates interstitial electrolyte and volume balance, this system may function as regulating blood pressure (BP). Thus, changes in lymphatic activity can be expected to alter systemic BP. We recently reported that increasing BP caused lymphatic endothelial dysfunction via oxidative stress in hypertension. In this study, we examined lymphatic contractile function in thoracic duct from 10-14-week-old Wister-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). No distinct morphological difference was observed in thoracic duct isolated from WKY and SHR (n=4). Thoracic duct from SHR exhibited enhanced contractile response to serotonin (5-HT) or endothelin-1 (ET-1) compared to age-matched WKY (5-HT: 127.8±19.7% vs 53.6±10.3% of KCl-induced maximum contraction, p<0.05, n=5). The augmented contraction in SHR was diminished by fasudil, ROCK inhibitor (p<0.05, n=4-5). Consistent with this, increased phosphorylation of myosin phosphatase targeting protein (MYPT) was observed in SHR thoracic duct. Expression of ROCK1 or ROCK2 was not changed in SHR thoracic duct. Next we examined lymphatic contractile function in 4-week-old SHR showing normal BP. Contractile response to 5-HT or ET-1 was not enhanced in young SHR compared to age-matched WKY (n=4). To examine if lymphatic dysfunction was associated with increased BP, we treated 4-week-old SHR with antihypertensive drugs (hydrochlorothiazide and hydralazine) for 6 weeks. This treatment completely blocked elevation of systolic BP (SBP) in SHR (p<0.05, n=5), but did not prevent the augmentation of lymphatic contraction (5-HT: 99.0±7.2% vs 98.1±14.5%, n=5). Interestingly, treatment of young SHR with losartan (Angiotensin II type 1 receptor [AT1R] blocker) for 6 weeks ameliorated the augmented contraction (5-HT: 137.4±12.7% vs 77.9±8.8%, p<0.05, n=5), while this treatment scarcely diminished the increase in SBP (152.0±8.7 mmHg vs. 177.2±10.9 mmHg, p<0.05, n=5). We conclude that lymphatic contractile function was significantly enhanced in adult hypertensive SHR, which is mediated by RhoA/ROCK pathway thorough activation of AT1R. The increase in lymphatic constriction may be involved in increased BP in hypertension through decreased lymphatic compliance.
Abstract P090: Nox5 Induces Vascular Damage Through C-src Activation In Human Hypertension
Authors: Camargo Livia L , Montezano Augusto C , Hussain Misbah , Wang Yu , Zou Zhiguo , Rios Francisco J , Neves Karla , Alves-lopes Rheure , Awan Fazli , Jensen Thomas , Hartley Richard , Touyz Rhian M
Published: September 2020

Nox5 is the major ROS-generating Nox isoform in human vascular smooth muscle cells (VSMC). The role of Nox5 in oxidative stress and redox signaling underlying vascular dysfunction in hypertension is unclear. We examined molecular processes that regulate VSMC Nox5-induced ROS generation, focusing on c-Src. VSMC isolated from small arteries from normotensive (NT) and hypertensive (HT) subjects were studied. Nox5 expression and phosphorylation (immunoblotting, immunoprecipitation); ROS generation (chemiluminescence); activation of contractile signaling pathways (immunoblotting), Ca
2+
influx (Cal-520AM fluorescence), reversible protein oxidation (cysteine sulfenic acid probe BCN-E-BCN), actin polymerization (phalloidin staining) and migration (wound healing assay) were assessed in absence/presence of Nox5 (melittin) and Src (PP2) inhibitors. To study Nox5-specific effects, we used p22phox-silenced VSMCs (siRNA). Vascular function in VSMC-specific Nox5 transgenic mice was studied by wire myography. In HT, ROS levels (139±27%), Nox5 expression (103±23%) and phosphorylation were increased (77±17.93%) (p<0.05, vs NT). Activation of c-Src (101±26%), PKC (96±33%), MLC
20
(416±71%) and Ang II-induced Ca
2+
influx (574±44 vs NT:451±26) were also increased in HT (p<0.05, vs NT). Melittin reduced Ang II-induced ROS generation in both groups (p<0.05 vs Ctl). In contrast, p22phox silencing increased ROS in both groups, an effect blocked by melittin (p<0.05 vs Ctl). Nox5 inhibition reduced Ang II-induced c-Src phosphorylation and oxidation. In HT, p22phox silencing was associated with sustained Ang II-induced PKC (83±21% vs Ctl) and MLC
20
(89±22% vs Ctl) phosphorylation, effects blocked by melittin and PP2 (p<0.05 vs Ctl). Nox5 and c-Src inhibition reduced Ca
2+
influx, actin polymerization and migration in HT. Hypercontractility observed in Nox5 mice was abolished by melittin and PP2. Our findings demonstrate that Nox5 is upregulated in human hypertension. This is associated with activation of c-Src, increased redox signaling and VSMC cytoskeletal reorganization, migration and vascular contraction. We define a novel Nox5-ROS-c-Src signaling pathway that may play a role in vascular remodeling/dysfunction in hypertension.
Abstract P098: Statins Relax Systemic Mesenteric Arteries Via The Inhibition Of Phosphodiesterases
Authors: Hasan Ahasanul , Zerin Farzana , Rahman Taufiq , Hasan Raquibul
Published: September 2020

Purpose:
Statins are the world’s most prescribed drugs with a range of vascular effects. Conventional view is that the vascular effects of statins are lipid-lowering-dependent and/or -independent, and both require long-term treatment. However, studies to examine direct vascular effects of statins are lacking as previous studies used supratherapeutic (≥1000-fold) concentrations of statins on non-resistance or cultured arteries that do not simulate physiology.

Methods:
Pressurized arterial myography, in-vitro phosphodiesterase (PDE) inhibition assay (colorimetric assay) and cGMP measurement using ELISA.

Results:
We found that, within 2-3 minutes of application, statins at 1nM produced mesenteric artery vasodilation that was reversed upon drug washout. Rosuvastatin and simvastatin produced vasodilation of ≥30μm while others dilated arteries by ≤20μm. Endothelium removal, or co-application of L-NAME, an inhibitor of endothelial nitric oxide (NO) synthase (eNOS), or ODQ, an inhibitor of smooth muscle cell guanylyl cyclase (sGC), or APC5, an inhibitor of protein kinase G (PKG), each inhibited statin-evoked vasodilation, suggesting the involvement of NO-sGC-PKG signaling axis. In contrast, mevalonate supplementation did not alter statin-induced vasodilation, precluding the role of lipid synthesis inhibition. To investigate potential involvement of phosphodiesterases (PDEs) that hydrolyze cGMP, we co-applied statins with a cGMP-specific PDE5 inhibitor sildenafil and found that statins indeed potentiated sildenafil-induced vasodilation. Our in-vitro PDE inhibition assay also showed that the vasodilatory statins have significant inhibitory actions on cGMP-dependent PDEs.

Conclusion:
Our study unveils a novel mechanism of systemic mesenteric artery vasodilation by statins. Future studies will examine if statins can be re-purposed for treating hypertension and/or erectile dysfunction.
Abstract P118: Antihypertensive Treatment Guided By Genetics: Pearl-ht, The Randomized Proof-of-concept Trial Comparing Rostafuroxin With Losartan
Authors: Citterio Lorena , Bianchi Giuseppe , Cusi Daniele , Ferrandi Mara , Lanzani Chiara Livia , Chiang Chern-en , Wang Kang-Ling , Ferrari Patrizia , Manunta Paolo
Published: September 2020

Primary hypertension contributes to more than 50% of all the worldwide cardiovascular deaths. Current antihypertensive therapy is still targeting the physiological mechanisms regulating blood pressure, but not the “causal” ones. So far, genetic studies have been unable to prove gene causation in human primary hypertension. In this study we compared a standard antihypertensive losartan treatment with a pharmacogenomics-guided rostafuroxin treatment in never-treated Caucasian and Chinese patients with primary hypertension (PEARL-HT trial registration: EudraCT: 2010-022073-34, ClinicalTrials.gov: NCT01320397). Rostafuroxin is a digitoxigenin derivative that selectively disrupts the binding to the cSrc-SH2 domain of mutant α-adducin and of the ouabain-activated Na-K pump at 10
-11
M. Of 902 patients screened, 172 were enrolled in Italy and 107 in Taiwan. After stratification for country and genetic background, patients were randomized to rostafuroxin or losartan, being the difference in the fall in Office Systolic Blood Pressure (OSBP) after two-month treatment the primary endpoint. Three pharmacogenomic profiles (P) were examined, considering: P1, adding to the gene variants included in the subsequent P2, the variants detected by post-hoc analysis of a previous trial; P2, variants of genes encoding enzymes for endogenous ouabain (EO) synthesis (
LSS
and
HSD3B1
), EO transport (
MDR1/ABCB1
), adducin (
ADD1
and
ADD3
); P3, variants of the
LSS
gene only. In Caucasians, the group differences (rostafuroxin 50 μg minus losartan 50 mg in OSBP mmHg) were significant both in P2 adjusted for genetic heterogeneity (P2a) and P3
LSS
rs2254524 AA [9.8 (0.6-19.0),
P
=0.038 and 13.4 (25.4-2.5),
P
=0.031, respectively]. In human H295R cells transfected with
LSS
A and
LSS
C variants, the EO production was greater in the former (
P
=0.038); this difference was abolished by rostafuroxin at 10
-11
M. Chinese patients had a similar drop in OSBP to Caucasians with losartan but no change in OSBP with rostafuroxin. These results show that the selective blockade of mutant adducin and endogenous ouabain pressor mechanisms by rostafuroxin improves the therapy of primary hypertension in in Caucasians carriers of the related gene variants.
Abstract P122: Lanosterol Synthase (LSS) Gene As Predictor Of Kidney Dysfunction In Hypertensive Patients
Authors: Simonini Marco , Faienza Sipontina , maggioni chiara maria , Citterio Lorena , Salvi Erika , Lanzani Chiara Livia , Messaggio Elisabetta , Fontana Simone , Cusi Daniele , Manunta Paolo
Published: September 2020

Recently we have proposed LSS as genotype-based risk stratification to predict accelerated eGFR decay in a prospective cohort study of essential HYP patients. We extract clinical data of a general population from HYPERGENES consortium. We also collect genetic data for LSS polymorphism that was already demonstrated as involved in kidney damage. A cohort of 3137 patients were selected. At different age, as expected, HYP status have a deep impact on eGFR. Indeed in young (age < 50ys) eGFR is higher in HYP vs control (86.2 ± 19.3 vs 82.7 ± 16.3 ml/min; p=0.04); vice-versa in elder (age > 65ys) HYP have a reduction in eGFR (55.7 ± 12.9 vs 71.0 ± 12.9 ml/min; p<0.001) and higher incidence of severe CKD (2.7% vs 0.1%; p=0.001). We do not observe a direct influence of LSS polymorphism of eGFR. When LSS is considered according to HYP status and age class it is possible to observe a preservation of age-associated eGFR reduction in normotensive patients (eGFR 91.4 vs 90.1 vs 81.8 at age classes for LSS risk allele); on the other side, LSS seems to enhance eGFR reduction associate to HYP status (eGFR 84.6 vs 75.6 vs 48.0 for LSS risk allele; p=0.032 after correction for covariates; see table for details and figure 1). Furthermore, our genomics lab just developed a LSS V642L Knock-in mouse model by CRISPR-Cas9 technique. The sequencing analysis confirmed the correct insertion of 643L mutation for both alleles in mice gene. The 642L LSS Knock-in mice at 1 month of age were viable, healthy and indistinguishable from the WT counterpart

Conclusion:
Patients caring the risk allele of this specific LSS polymorphism seems to express hyper-filtration if compared to their counterparts.
Abstract P127: Sex-differences In The Association Of
TMEM27
Variants With Hypertension Traits
Authors: Franceschini Nora , Le Thu H
Published: September 2020

Introduction:
The global deletion of collectrin encoded by the
TMEM27
gene leads to endothelial dysfunction, salt sensitivity and hypertension. To translate experimental findings to population studies, we studied the association of single nucleotide polymorphisms (SNPs) with blood pressure (BP) traits.

Methods:
We examined the SNP associations within
TMEM27
with BP traits in 11,926 Hispanics/Latinos. BP was measured during a clinic visit and two measures were averaged. Genotypes were imputed from 1000 Genomes Project (1000G). Analyses were stratified by sex, given
TMEM27
is located on the chromosome X. We used linear or logistic mixed models for association analyses with systolic and diastolic BP, or hypertension, respectively, in models adjusted for age, body mass index, relatedness and population stratification.

Results:
The mean age was 46 years-old (standard deviation 14), 41% were men, 28% had hypertension (BP> 140/90 mm Hg). Two intronic SNPs were associated with BP traits in men but not women, when adjusting for multiple testing (Table). SNP rs5936004 associated with lower diastolic BP is more common in Admixed Americans in the 1000G samples (minor allele frequency [MAF] 0.15), and low frequency in European and African ancestry (0.02 and 0.04). SNP rs183583165 is more common in 1000G African sample (MAF 0.03) but rare in other populations. These SNPs were not in linkage disequilibrium with SNPs in the nearby
ACE2
gene, which has a role in BP control.

Conclusion:
This study identified associations of
TMEM27
SNPs with BP traits in Hispanic/Latino men but not women, for variants present in higher frequency in Amerindian and African ancestries.
Abstract P134: ASSOCIATION OF HYPERTENSION WITH MORTALITY RISK IN PATIENTS WITH COVID 19 PNEUMONIA IN A HOSPITAL IN MEXICO CITY
Authors: Alanís Naranjo José Martín , Olguín Contreras Gabriela , Ibarra Jaimes Cristo Raymundo
Published: September 2020

Introduction:
The world is currently suffering from the outbreak of a pandemic caused by the SARS-CoV-2 coronavirus, which causes the disease called COVID-19. This disease was reported for the first time in Wuhan, Hubei Province, China, on December 31, 2019. Hypertension, diabetes and cardiovascular disease are common among patients with COVID-19. In Mexico, information on the association between COVID-19 and hypertension is scarce.

Methods:
This investigation was a descriptive, observational and cross-sectional study that included patients over 18 years of age who had been hospitalized with laboratory-confirmed COVID-19 between April 6, 2020, and May 6, 2020, and exhibited chest X-ray abnormalities (ground-glass opacity, interstitial alterations and/or multilobar infiltrate). Severity of pneumonia (severe vs. nonsevere) at the time of admission was defined using the community-acquired pneumonia guidelines of the American Thoracic Society (ATS).

Results:
Information was collected from 89 patients with COVID-19 pneumonia, 34 of whom (38.2%) were hypertensive. When studying risk factors in hypertensive patients and their degree of statistical association with risk of mortality, only the severity of pneumonia stood out. The association between severe pneumonia and mortality was statistically significant (OR: 10.9, CI 1.19-99.6, p value = 0.034).

Conclusions:
Severity of pneumonia upon admission can be regarded as a marker of adverse clinical outcome in hypertensive COVID-19 patients. Among hypertensive COVID-19 patients, in-hospital mortality was high (68%); such mortality was higher in our study than has been reported in other series worldwide.
Abstract P141: Immunosuppressant Treatment Attenuates Augmentation Of Intrarenal NLRP-3 Inflammasome In Angiotensin II-dependent Hypertension
Authors: Satou Ryousuke , Franco Martha G , Katsurada Akemi , Dugas Courtney M , NAVAR L G
Published: September 2020

Activated inflammasomes enhance maturation of pro-inflammatory cytokines, which facilitates the development of kidney injury. NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3), one of major subunits in the inflammasome complex, plays a crucial role in innate immunity and inflammation. Although NLRP3 inflammasome is activated by ATP-P2Y7 axis and reactive oxygen species, the expression of pro-NLRP3 is promoted by NF-κB activated by cytokines or PAMPs/DAMPs. Thus, we hypothesized that mycophenolate mofetil (MMF), an immunosuppressant, attenuates augmentation of intrarenal NLRP3 and consequent progression of kidney injury in angiotensin II (Ang II)-dependent hypertension. Ang II (80 ng/min) was infused with/without daily MMF administration (50 ng/kg) to Sprague-Dawley rats for 2 weeks. mRNA levels of intrarenal NLRP3 and AIM2, which forms another type of inflammasome complex by viral or bacterial infections, were measured by droplet digital PCR. Furthermore, kidney injury was evaluated. MMF treatment mitigated Ang II-induced macrophage infiltration into kidneys, suggesting immunosuppression by the drug. Ang II infusion significantly increased intrarenal NLRP3 mRNA levels (normotensive control group: 4.12±1.1 copies/ng RNA vs. Ang II-infused group: 9.96±1.8 copies, N=5). The elevated NLRP3 expression in kidneys of Ang II-infused rats was attenuated by MMF treatment (6.24±1.4 copies). In contrast, intrarenal AIM2 levels were lower than NLRP3 in the control group and the levels were not altered by Ang II infusion or MMF treatment (normotensive control group: 0.42±0.1 copies, Ang II-infused group: 0.35±0.06 copies and Ang II+MMF group: 0.35±0.08 copies). Urinary protein and angiotensinogen levels were elevated in Ang II-infused rats and MMF treatment suppressed the augmentations. Histological analyses also showed the development of kidney injury including mesangial expansion and tubulointerstitial fibrosis observed in the hypertensive rats, but these injury markers were mitigated by MMF. These results demonstrate activation of the NLRP3 inflammasome in Ang II dependent hypertension and indicate that immunosuppression by MMF mitigates the inflammasome activation, which contributes to attenuation of the kidney injury.
Abstract P147: Attenuation Of Diuretic And Natriuretic Responses To Acute Saline Volume Expansion In Mice Pre-treated With Tumor Necrosis Factor-alpha (TNFα) Inhibitor, Etanercept.
Authors: Majid Dewan S , Castillo Alexander
Published: September 2020

High salt intake induces an immune response that activates the mononuclear phagocyte system (MPS) cells to produce TNFα. We have previously demonstrated that intravenous infusion of TNFα in mice induces diuresis and natriuresis by inhibiting renal tubular sodium reabsorption. We hypothesize that the intravenous saline infusion can also induce the production of TNFα from MPS cells and such increase in TNFα influences saline induced natriuresis in the kidney. To examine this hypothesis, we measured the changes in TNFα levels in plasma and in urinary excretion rate (U
TNFα
V) during intravenous infusion of isotonic saline (0.9% NaCl), first at euvolemic condition (3 μL/min for 60 min; Baseline period) and then at an enhanced infusion rate (12 μL/min for 90 min; Volume expansion period) in anesthetized mice (n=5). Renal blood flow (RBF) and glomerular filtration rate (GFR) were measured by PAH and inulin clearances respectively. TNFα concentration in plasma and urine samples were determined using ELISA kit (Ebioscience, Woburn, MA). TNFα level in plasma collected during baseline period was undetectable, however, TNFα was increased to 3.7±1.3 pg/mL during volume expansion (VE) period. Baseline U
TNFα
V level was 0.01±0.002 pg/min/g (kidney wt), which was increased to 0.11±0.03 pg/min/g (P<0.05) during VE period. VE increased urine flow (V, 5.4±0.5 to 22.0±5.1 μL/min/g; P<0.05) and sodium excretion (U
Na
V; 0.54±0.19 to 4.84 ±1.16 μmol/min/g; P<0.05) without significant changes in RBF (7.1±1.0 to 6.0±1.8 mL/min/g) and GFR (1.18±0.11 to 0.94±0.28 mL/min/g). Interestingly, the diuretic and natriuretic responses to VE were markedly attenuated in mice (n=5) pretreated with a TNFα inhibitor, etanercept (ETN; 0.5 mg/kg intraperitoneally once daily for 3 days prior to the experiment day). VE induced changes in ETN treated mice are as follows: V, 5.9±0.65 to 7.9 ±1.6 μL/min/g; U
Na
V, 0.43±0.6 to 1.1±0.28 μmol/min/g; RBF, 5.4±0.4 to 6.6±0.9 mL/min/g and GFR, 0.87±0.09 to 0.98±0.13 mL/min/g. These findings demonstrate for the first time that an intravenous saline volume infusion resulted an increase in TNFα level in plasma and in urine. These results strongly suggest a physiological role for TNFα in regulating renal excretory function during saline volume expansion.
Abstract P155: Phenotyping The Association Between Nocturia And Hypertension: A Systematic Review And Meta-analysis
Authors: Rahman Syed N , Cao Daniel J , Monaghan Thomas F , Flores Viktor X , Moy Matthew W , Vaysblat Michael , Lazar Jason M , Weiss Jeffrey P
Published: September 2020

Introduction:
The association between nocturia and hypertension has been widely reported, yet remains poorly characterized, precluding a more refined understanding of blood pressure as it relates to the clinical urology setting. We synthesized current evidence on the relationship between nocturia and hypertension as a function of nocturia severity, age, sex, race, and diuretic use.

Methods:
We searched PubMed, EMBASE, and Cochrane databases for studies published up to May 2020. Random effects meta-analyses were performed to identify the pooled odds ratio (OR) for nocturia given the presence of hypertension. Meta-regression and subgroup analyses were performed to identify differences across demographic factors. We applied the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies to evaluate the quality of evidence.

Results:
Of 1530 identified studies, 23 met the criteria for inclusion. The overall pooled OR for the association of hypertension with nocturia was 1.26 (95% CI 1.22-1.29, p<0.001). Pooled estimates were 1.21 (1.16-1.25, p<0.001) and 1.31 (1.26-1.36, p<0.001) using a 1- and 2-void cutoff for nocturia, respectively (p<0.001 between cutoffs). The association was stronger in females compared to males (1.41 [1.29-1.53] vs. 1.26 [1.20-1.32], p<0.001), and in African-American (1.56 [1.25-1.94]) and Asian (1.28 [1.24-1.32]) versus Caucasian populations (1.16 [1.09-1.24]) (p<0.05for both). Age and diuretic use had no observable effect on the association between nocturia and hypertension.

Conclusions:
There exists an increased odds of nocturia in hypertensive individuals. This association is stronger following a higher nocturia cutoff, in females, and in some racial subgroups, but unrelated to age and diuretic utilization.
Abstract P156: Improvement In Blood Pressure Using Remote Patient Monitoring During COVID19
Authors: Liyanage-Don Nadia A , Schwartz Joseph E , Moise Nathalie , Bryant Kelsey B , Bono Adina , Kronish Ian M
Published: September 2020

Introduction:
The coronavirus disease 2019 (COVID19) pandemic required strict social distancing to curb transmission. Unfortunately, these measures severely limited healthcare access and chronic disease management. In response, many health organizations rapidly developed or expanded telemedicine to provide care directly to patients at home. Little has been reported about the impact of such interventions on clinical outcomes during COVID19. We examined whether enrollment in a remote patient monitoring (RPM) program for hypertension (HTN) prior to COVID19 was associated with improved blood pressure during the pandemic.

Methods:
We developed an RPM program that tracked vital signs, medication side effects, and treatment adherence patterns outside of the clinic. Patients were referred by their primary care doctor for uncontrolled HTN or suspected white coat HTN. Patients received a two-way tablet, blood pressure cuff, and virtual nursing support via scheduled video visits. Those referred for uncontrolled HTN who had at least two weeks of data both before and after the onset of COVID19 (defined as the first two weeks of March 2020) were included in the study. A mixed-models analysis that adjusted for serial autocorrelation was used to compare mean systolic blood pressure (SBP) and mean diastolic blood pressure (DBP) in the pre-/post-COVID19 periods.

Results:
Of 94 patients enrolled in the RPM program to date, 46 had at least two weeks of data both pre-COVID19 and post-COVID19. Mean age was 69.0 ± 10.9 years, 69.6% (32 of 46) were women, 78.3% (36 of 46) were Hispanic, and 63.0% (29 of 46) were Spanish-speaking. Pre-COVID, mean SBP was 132.31 ± 13.99 mmHg, mean DBP was 77.10 ± 9.87 mmHg, and 70% (32 of 46) of patients had uncontrolled BP (>130/80 mmHg per AHA guidelines). Post-COVID, mean SBP was 129.57 ± 13.29 mmHg, mean DBP was 76.00 ± 9.16 mmHg, and 57% (26 of 46) of patients had uncontrolled BP. There was a significant reduction in both mean SBP (β = –2.74, 95% CI –5.21, –0.26, p = 0.03) and mean DBP (β = –1.10, 95% CI –2.22, 0.02, p = 0.05) post-COVID vs. pre-COVID.

Discussion:
Despite the stress and social isolation associated with COVID19, participation in an RPM program that combines home BP monitoring with virtual nursing support can help maintain and even mildly decrease BP.
Abstract P164: Self-reported Use Of Recommended Calcium Channel Blockers And Diuretics In Non-hispanic Blacks With Hypertension: An Opportunity To Improve Evidence-based Prescribing
Authors: Egan Brent M , Yang Jianing , Rakotz Michael , Sutherland Susan E , Wozniak Gregory
Published: September 2020

Background:
Non-Hispanic Blacks (NHBs) have a higher prevalence of hypertension and incidence of cardiovascular events than NH(W)hites and Hispanics. To improve hypertension control and outcomes in NHBs, the U.S. High Blood Pressure (BP, mmHg) Guidelines recommended calcium channel blockers (CCBs) and diuretics over other drug classes as initial therapy in 2014 and 2017. Among adults with hypertension, percentages of NHBs who reported taking CCBs and diuretic monotherapy before and after 2014 were assessed and compared to NHWs and Hispanics.

Methods:
National Health and Nutrition Examination Surveys data in 2-year cycles from 2007-2012 and 2015-2018 were analyzed and included self-identified NHB, NHW, and Hispanic adults ≥18 years with recorded BP values and hypertension defined as self-reported BP medication use in the previous month, which included medication class, e.g., CCBs and diuretics. Multivariable logistic regression was used to assess the independent contribution of NHB race/ethnicity to prevalence of CCB and diuretic use as monotherapy.

Results:
Self-reported CCB or diuretic monotherapy did not increase significantly from 2007-2012 to 2015-2018 among NHBs (44% vs. 50%, p=0.12) or Hispanics (22% vs 29%, p=0.12) and a non-significant decline in NHWs (26% vs 22%, p=0.14). NHBs were more likely to report taking CCBs or diuretics as monotherapy than NHWs or Hispanics in both time periods (p<0.001). In multivariable analysis, NHBs were more likely to report taking a CCB (multivariable odds ratios 3.57 [95% confidence interval 2.6-4.9]) and diuretic monotherapy (1.63 [1.2-2.3]) than NHWs.

Conclusions:
NHBs had a non-significant increase in self-reported CCB or diuretic as monotherapy from 2007-2012 to 2015-2018, suggesting limited impact for this prescribing recommendation in the 2014 and 2017 High BP Guidelines. NHBs more often reported CCB or diuretic monotherapy than NHWs and Hispanics in both time periods, suggesting some clinicians were aware of evidence prior to the 2014 Guideline. Yet, half of NHBs did not report taking CCBs or diuretics as monotherapy in 2015-2018, indicating further opportunity to prescribe evidence-based initial therapy in NHBs that could improve BP control, cardiovascular outcomes and health equity.
Abstract P180: Effect Of Sunitinib Treatment On Skin Sodium Accumulation In Patients With Metastatic Renal Cancer: A Pilot Study
Authors: Marko Lajos , Dörr Anne , Linz Peter R , H. van den Meiracker Anton , Kühne Titus , Dechend Ralf , Danser Jan H , Flörcken Anne , Mueller Dominik N
Published: September 2020

Angiogenesis is required for invasive tumor growth and metastasis which is controlled mainly by vascular endothelial growth factors (VEGF). Novel strategies for cancer treatment target VEGF signaling. These agents are featured by adverse events including hypertension. New concepts suggest that besides the kidneys, the skin also plays a role in body sodium homeostasis and blood pressure regulation by a VEGF-C–dependent buffering mechanism. Here, we tested the hypothesis that changes in blood pressure correspond to tissue sodium accumulation during sunitinib treatment of metastatic renal cell carcinoma patients (https://clinicaltrials.gov/identifier: NCT04368546; Charité ethical approval EA1/044/15).Male patients (n=4) took sunitinib according to the standard treatment protocol, 50 mg once daily, taken for 4 weeks followed by a 2-weeks off treatment period. Measurements were performed at baseline (before sunitinib treatment), and over a complete on-off-on period. Tissue sodium content was measured using non-invasive 23Na-MRI; skin sodium was measured in a group (n=5) of age-matched healthy subjects, as well. Blood pressure was measured according to AHA guidelines. Blood withdrawal followed after ca. 45 minutes of sitting to measure VEGF-A, VEGF-C, endothelin-1, renin and aldosterone levels.Elevated systolic blood pressure under sunitinib treatment decreased to the baseline level in the off-treatment phase (130.5 mmHg vs 117.5 mmHg, respectively, p<0.05). Plasma endothelin-1 levels mirrored directly and VEGF-A levels inversely the blood pressure changes. Baseline skin sodium content was similar to the skin sodium level of healthy controls. Skin sodium content was elevated after the first on-treatment phase and stayed high in all the following measurements in comparison to control subjects. Patients had high baseline VEGF-C levels that decreased after the first treatment with sunitinib and stayed low independently of further treatment phase.In conclusion, sunitinib treatment suppresses VEGF-C levels permanently which is associated with sustained elevated skin sodium levels. Furthermore, we confirmed the association between plasma endothelin-1 levels and blood pressure changes during sunitinib treatment protocol.
Abstract P201: Evaluating Data Sharing And Privacy Policies Of Diabetes Mobile Apps: Where Is The Data Going?
Authors: Abdelrahman Khaled , Bilello Josh , Panchbhavi Megna , Abdullah Mohammed S
Published: September 2020

Introduction:
Diabetes mobile applications (apps) that help patients monitor disease have led to privacy concerns. We aimed to assess privacy policies for diabetes mobile applications with a focus on data transmission to outside parties.

Methods:
The App Store was used to gather apps pertaining to diabetes by searching “diabetes” and “blood sugar”. Two readers evaluated privacy policies (PP) including data sharing and storing techniques for mention of 27 predetermined criteria. All network traffic generated while loading and using the app was intercepted by a man-in-the-middle attack to listen to data delivered between the sender and receiver of data transmissions. A packet analyzer determined contents of transmission, where data was sent, and if transmission contained user data.

Results:
Of 35 apps evaluated, 29 (83%) had PP. The most frequent transmission destinations were Google (n=130 transmissions), Kamai Technologies (n=53), Facebook (n=38) and Amazon (n=33). 35 of 35 apps (100%) were transmitting data to a third party. 2 of 2 (100%) of those who had a privacy policy without mention of a third party transmitted data to a third party. 8 of 8 (100%) apps who mentioned they would not transmit to a third party were found to do so. 19 of 19 (100%) apps who mentioned they would transmit data to a third party were found to do so. All apps (n=6) without a privacy policy were found to be transmitting data to a third party.

Conclusion:
Most diabetes apps on the App store have accessible PP. All apps evaluated transmitted data to a third party, even when the policy stated this would not occur. As mobile applications are increasingly utilized by patients, it is important to warn of privacy implications.