bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P196: Hot Yoga and Hypertension: Exploration of a Novel Lifestyle Intervention
Authors: Hunter Stacy , Fadeyi A. Tobi , Shadiow James
Published: September 2019

The practice of hot yoga is becoming widespread as marked by a growing number of yoga studios offering classes in heated rooms ranging in temperature from 27 to 41°C. Previous research has shown reductions in ambulatory blood pressure (BP) with thermoneutral (nonheated) yoga interventions; however, to date, no studies have investigated the safety and efficacy of hot yoga in hypertension (HTN). The purpose of this ongoing trial is to determine whether hot yoga can reduce ambulatory BP, augmentation index (AIx), and perceived stress in unmedicated adults with elevated BP and stage I HTN. Sedentary men and women (ages 20-65yrs) were enrolled if the averages of 3 seated BP measurements were within the elevated BP (120-129 mmHg for systolic with a diastolic <80 mmHg) or stage I HTN (130-139 mmHg for systolic or 80-89 mmHg for diastolic BP) ranges at two separate visits. Twenty-four hours of ambulatory BP monitoring was completed prior to randomization to the yoga or control groups. Yoga group participants (n=5) completed 3 60min Bikram yoga classes (40.5°C) and the control group (n=5) was instructed not to change their physical activity for 12 weeks. AIx and perceived stress were assessed using the SphygmoCor and Perceived Stress Scale (PSS). Most study participants were African-American (n=3) or Hispanic/Latinx (n=3) and no adverse events occurred. Twenty-four-hour systolic (126±17 to 121±14 mmHg; p=0.01) and diastolic (82±12 to 79±12 mmHg; p=0.04) BPs and PSS scores (14±9 to 10±6; p=0.047) were reduced following the yoga intervention. When comparing waking versus sleeping BPs according to subjects’ reported sleep times, only waking systolic (129±15 to 122±15 mmHg; p=0.016) and diastolic (85±11 to 81±12 mmHg; p = 0.024) BPs declined while no changes in sleeping BPs were detected in the yoga group. AIx (23% to 21%; p =0.58) and body mass were unaltered following the yoga intervention and no outcome variable changed in the control group. Preliminary results support the safety and efficacy of hot yoga in improving ambulatory BP and reducing mental stress, a correlate of HTN, in adults with elevated BP and stage I HTN. These BP reductions were observed in the absence of BP medications or weight loss, and do not appear to be associated with improvements in pulse wave analysis.
Abstract P2001: Nicotinamide Riboside the New Promising Drug of Myocardial Infarction Management
Authors: Tannous Cynthia , Ghali Rana , Habeichi Nada , Jurjus Abdo , Mericskay Mathias , Refaat Marwan , Zouein Fouad
Published: September 2019

Introduction:
Myocardial infarction (MI) is the major cause of death worldwide. Nicotinamide-Adenine-Dinucleotide (NAD) is emerging as a metabolic target being a major coenzyme in mitochondrial oxidation and oxidative phosphorylation and a substrate of Sirtuins and PARPs, critical enzymes for cardiac remodeling. Altered NAD homeostasis is reported in several models of heart failure including MI with a striking upregulation of Nicotinamide-Riboside-Kinase2 (NMRK2) and a decrease of NAD levels. NMRK2 requires Nicotinamide Riboside (NR) as a substrate to produce NAD. In this study, we hypothesized that stimulating NMRK2 pathway by NR supplementation will upregulate NAD synthesis and subsequently improve metabolic state and cardiac function post-MI.

Methods:
MI was induced by the left anterior descending coronary artery ligation in 2-3 months old male mice. Echocardiography was performed at baseline, day 1, and day 4 following MI. At sacrifice, cardiac genes expression was evaluated by RT-qPCR and myocardial NAD levels were determined using a colorimetric assay. Histologically, Masson-Trichrome was performed on cardiac sections to assess cardiac fibrosis.

Results:
RT-qPCR analysis showed a 60 fold increase of Nmrk2 expression levels (P&it0.01) 4 days following MI. This upregulation was highlighted by the boost of NAD levels (708.81±79.83 pmoles/g of tissue in the MI-NR group vs 394.12 ±84.04 pmoles/g of tissue in the control group (p&it0.05)). Following MI, mitochondrial SIRT3 expression dropped by 40% and NR restored those levels which are critical for mitochondrial biogenesis. NR treatment markedly decreased the expression of PARP1 (1.22±0.34 in MI-NR group vs 2.69±0.45 in MI group (p&it0.05)), a well-known consumer of NAD. Histologically, fibrosis levels significantly dropped 4 days following NR treatment when compared to non-treated MI group (11±2,72 u.a vs 18±1,98 u.a, p&it0.05).

Conclusion:
NR treatment improves myocardial metabolic impairment, but not myocardial function, as early as 4 days following MI when compared to relative control groups. Additional experiments are underway to reveal the impact of NR treatment on cardiac remodeling and function at 7 days post-MI.
Abstract P2004: Neural Inflammation in Stellate Ganglia Mediates Lung Injury-Induced Arrhythmogenesis
Authors: Adam Ryan , Gao Lie , Hong Juan , Zucker Irving H , Lisco Steven J , Wang Hanjun
Published: September 2019

Background:
People who suffer lung injury, incurred through a variety of means, are at greatly increased risk of developing cardiac arrhythmias. Treatment options remain limited. We propose that stellate ganglia neuro-inflammation contributes to lung injury-induced arrhythmogenesis.

Methods:
We created lung injury in adult Sprague-Dawley rats by a single tracheal instillation of Bleomycin (Bleo, 2.5 mg/kg), and used Saline instillation as a control. We recorded ECGs in conscience, freely moving Bleo and Saline rats treated with and without oral minocycline (20 mg/kg/day for 4 weeks, an anti-inflammatory drug to inhibit microglia/macrophage activation) using implantable radio-telemeters. During terminal experimentation we investigated the effect of minocycline on isolated electrical stellate stimulation-induced cardiac arrhythmias in Bleo rats.

Results:
Bleo rats exhibited lung lesions at necropsy and lung fibrosis histologically. Bleo rats, on average, had more premature ventricular contractions (PVCs) than Saline rats, an effect largely prevented by chronic treatment with minocycline. (PVC data 1-wk post Bleo: Saline 22±12, Bleo 481±394*#, Bleo+Mino 24±9. PVC data 2-wks post Bleo: Saline 6±2, Bleo 255±165*, Bleo+Mino 21±8. Data are AVG±SEM number of PVCs over 24-hr, n=5-6 for all groups. *P<0.05 between Bleo vs. Saline, #P<0.05 Bleo vs. Bleo+Mino). Isolated electrical stellate ganglia stimulation caused a frequency-dependent increase in heart rate without arrhythmias in normal rats but in Bleo rats triggered a significant number of PVCs, indicating stellate ganglia excitability post lung injury. This effect was greatly reduced in Bleo rats receiving minocycline. Since our isolated stellate preparation is decentralized, these data clearly suggest a local protective effect of minocycline on stellate ganglia in Bleo rats. Immunofluorescence data suggested that compared to sham-operated rats, the number of Iba-1-positive (a macrophage marker) cells in stellate ganglia of bleomycin-treated rats was significantly increased at 1 week post lung injury and lasted for at least 4 weeks.

Conclusion:
Our data showed that stellate ganglia neuroinflammation contributes to arrhythmogenesis in our Bleo lung injury rat model.
Abstract P2016: Proximal Tubule-Specific Knockout of Angiotensin II Type 1a Receptors in the Kidney Augments the Natriuretic Response to Angiotensin III in Mice
Authors: Zhao Chunling , Li Xiao C , Chen Xu , Zheng Xiaowen , Zhuo Jia L
Published: September 2019

Angiotensin III (ANG III), a major metabolite of the potent vasopressor hormone ANG II, reportedly binds and activates AT
2
receptors to oppose the AT
1
receptor-mediated antinatriuretic effect of ANG II in the proximal tubules of the kidney. The present study tested the hypothesis that global (

Agtr1a
-/-

) or proximal tubule-specific deletion of AT
1a
receptors in the kidney (PT-

Agtr1a
-/-

) attenuates the blood pressure, but augments renal Na
+
excretory responses to ANG III in mice. Proximal tubule AT
1a
receptor knockout mice (PT-

Agtr1a
-/-

) were generated using the Sglt2-Cre/
Agtr1a
-floxed approach. Adult male wild-type littlemates (WT), global (

Agtr1a
-/-

), and PT-

Agtr1a
-/-

mice (n =7-10 for each group) were anesthetized and infused with saline or increasing doses of ANG III, at 10, 50, and 100 ng/min,
i.v
., respectively, for 60 min each. An additional group of PT-

Agtr1a
-/-

mice (n=7) was infused with ANG III at 1.5 mg/kg/day,
i.p
., via osmotic minipump for 2 weeks. Basal systolic, diastolic, and mean arterial blood pressure were significantly lower (
p
<0.01), whereas 24 h urinary Na
+
excretion was significantly higher in

Agtr1a
-/-

and PT-

Agtr1a
-/-

than WT mice (
p
<0.01). ANG III significantly increased systolic blood pressure from 82 ± 5 mmHg to 116 ± 8 mmHg in anesthetized WT mice (n=8,
p
<0.01
vs.
baseline), and from 75 ± 3 mmHg to 109 ± 6 mmHg in anesthetized PT-

Agtr1a
-/-

mice (n=10,
p
<0.01
vs.
baseline). There was no significant difference in the net pressor response to ANG III between WT and PT-

Agtr1a
-/-

mice. A similar pressor effect to ANG III was confirmed in conscious PT-

Agtr1a
-/-

mice (Basal: 97 ± 2 mmHg vs. ANG III: 111 ± 5 mmHg, n=7,
p
<0.05). Global deletion of AT
1a
receptors completely blocked the pressor effect of ANG III in

Agtr1a
-/-

mice (n=7,
p
<0.05
vs.
WT or PT-

Agtr1a
-/-

mice). In WT mice, ANG III induced small, but significant, antinatriuretic responses at 10 and 50 ng/min (
p
<0.05), respectively. Conversely, ANG III induced small, but significant, natriuretic responses at 50 and 100 ng/min in PT-

Agtr1a
-/-

mice (
p
<0.05). These results suggest that the pressor effect of ANG III is mediated by systemic AT
1a
receptors, whereas the natriuretic effect of ANG III in PT-

Agtr1a
-/-

mice may involve AT
2
receptors in the proximal tubules of the kidney.
Abstract P2020: Effect of Steroid Hormones on Catalytic Activity of Renin Angiotensin Aldosterone System Enzymes and on Cell Behaviour in Human Mesangial Cells
Authors: Stoll Danielle , Casarini Dulce E
Published: September 2019

Aldosterone (Aldo) and glucocorticoids are steroid hormones reported to induce several responses in human mesangial cells (MC), essential cells for the maintenance of glomerular structure and filtration. Alterations in these cells may result in numerous diseases such as hypertension, diabetes and lupus nephritis. Renin Angiotensin-Aldosterone System (RAAS) was reported to have a role in physiological functions such as modulate differentiation, proliferation and apoptosis. Since MC have a relevant role for the maintenance of a health glomerular environment and the catalytic activity of RAAS enzymes are fundamental for biologically active peptides generation, we decided to study the effects of aldosterone and dexamethasone (Dexa) in the modulation of RAAS enzymes activities and how these modulations may influence in MC behaviour. Cell viability assay showed that after 24h of spironolactone (SPI) stimulus MC viability increased in comparison to control cells, as well as the combination of SPI+Aldo. When only aldosterone was added as stimulus, alterations in viability were not found. Dexa treatment also increased cell viability, but the following combination Aldo+Dexa, SPI+Dexa and SPI+Aldo+Dexa did not result in viability alterations which may indicate that dexamethasone needs to binding Aldo receptor to increase MC viability. ACE catalytic activity decreased in MC medium when these cells were exposed to Dexa and Aldo+Dexa for 4h and compared to positive control (Angiotensin II; Ang II) and SPI. After 24h, MC lysates exposed to Aldo showed an increase in ACE activity in relation to Ang II and Aldo+Dexa which, may indicate a protective effect of dexamethasone against the deleterious effects of aldosterone. ACE 2 activity increased in MC lysates exposed to SPI for 24h in comparison to control cells. Immunofluorescence assay demonstrated alteration in collagen type IV (CIV) expression. SPI treatment increased CIV expression in comparison to all groups while Aldo+Dexa showed a decrease in CIV expression compared to control cells. Isolated stimulus with Aldo or Dexa demonstrated similar stain pattern with control. To date, we can conclude that steroids hormones induce modulations in ACE and ACE 2 activity and in CIV expression.
Abstract P2024: Treatment of Primary Hyperaldosteronism Increases Plasma Epoxyeicosatrienoic Acids
Authors: Luther James M , Adler Gail , Wei Shouzuo , Nian Hui , Yu Chang , Brown Nancy J
Published: September 2019

Epoxyeicosatrienoic acids (EETs) are lipid signaling molecules formed from arachidonic acid by the action of CYP450s. EETs cause vasodilation, exert anti-inflammatory effects, and enhance insulin secretion and sensitivity. 14,15-DHET has been reported to be increased in patients with hyperaldosteronism, but the effects of aldosteronism on EETs and sEH activity are unknown. We tested the hypothesis that treatment of hyperaldosteronism would alter EET concentrations. We studied 9 patients with biochemically confirmed hyperaldosteronism before and after unilateral adrenalectomy (6) or treatment with a mineralocorticoid (MR) antagonist. Aldosterone decreased significantly from 20.4±15.2 to 6.2±3.7 ng/mL following treatment, but cortisol did not change. Circulating total EET concentrations increased from 11.9±5.9 to 18.5±12.6 nM with treatment of primary hyperaldosteronism. Among the regioisomers of EETs, 14,15-EET significantly increased after treatment, whereas 11,12-EET and 8,9 EET did not change significantly (
Figure
; • adrenalectomy, ○ MR antagonist). EET concentrations increased in patients treated with an MR antagonist as well as those treated by surgical resection. Total DHET concentrations and specific regioisomers of DHET did not change significantly with treatment. Circulating total EETs (r=-0.52,
p
=0.026), 14,15-EET (-0.56,
p
=0.015) and 11,12-EET (r=-0.48,
p
=0.042) correlated inversely with aldosterone. We report for the first time that circulating EET concentrations increase following treatment of primary hyperaldosteronism.
Abstract P2027: Preliminary Characterization Of The
125
I-angiotensin 1-7 Binding Site In Rat Liver
Authors: Stoyell-conti Filipe F , Itty Sarin , Asif Mahnoor , Stewart Hanna , Abraham Christy , West Crystal , Speth Robert C
Published: September 2019

Angiotensin 1-7 (Ang 1-7) is a product of the renin-angiotensin system (RAS) that can reduce blood pressure and fibrosis. For more than a decade Mas has been viewed as the receptor for Ang 1-7, however, there are lingering doubts regarding the nature of the interaction between the heptapeptide and Mas. To date, no one has pharmacologically characterized Ang 1-7 binding in tissue membrane preparations. In this study we show that
125
I-Ang 1-7 binds to a site for which Ang 1-7 has low (μmolar) affinity, suggesting that the addition of an iodine molecule to the tyrosine in position 4 of Ang 1-7 drastically changes the characteristics of this peptide making it unsuitable for characterization of Ang 1-7 receptors.
125
I-Ang 1-7 binds with moderately high affinity (10-20 nM) and saturability to a binding site in rat liver membranes that is displaceable by
127
I-Ang 1-7 (iodoAng 1-7) at nanomolar concentrations. This binding is also displaceable by inhibitors of metalloproteases. To test the hypothesis that
125
I-Ang 1-7 binds to a peptidase, a series of peptidase inhibitors were evaluated for their ability to inhibit
125
I-Ang 1-7 binding. The non-selective matrix metalloprotease (MMP) and A Disintegrin And Metalloprotease (ADAM) inhibitors marimastat, batimastat, and GM-6001, which inhibit MMP1,2,3,7,8,13,14 and ADAM 9,17, partially inhibited
125
I-Ang 1-7 binding with nanomolar affinities, similar to their IC
50
values for MMPs, suggesting that
125
I-Ang 1-7 binds to MMPs and/or ADAMs as well as other tissue elements. Further testing with the specific MMP-2 (ARP100), MMP-9 and ADAM-17 inhibitors indicate that
125
I-Ang 1-7 is not binding to these peptidases. Continuing studies are underway to establish conditions under which the
125
I-Ang 1-7 ligand is not metabolized by peptidases, while retaining the ability to bind to peptidases is underway to enable the identification of the specific peptidase(s) or other binding moieties to which
125
I-Ang 1-7 binds to determine their potential therapeutic importance as a druggable targets.
Abstract P2028: Paracrine And Intracellular Angiotensin II Activate Protein Kinase C, Map Kinase Erk1/2, And Nuclear Factor-кB Signaling Responses In Murine Glomerular Mesangial Cells.
Authors: Leite Ana P , Li Xiao C , Casarini Dulce E , Zhuo Jia L
Published: September 2019

The glomerular mesangial cells (MC) are a key target for the endocrine, paracrine, autocrine, and intracrine angiotensin II (ANG II). Increased local paracrine and intracrine ANG II formation in MCs may cause glomerular injury by promoting MC cell growth, hypertrophy and fibrosis. In the present study, we investigated the phospho-proteomic signaling and mitochondrial responses to paracrine or intracellular ANG II in murine MCs. MCs were grown to ~80% confluence in 6-well plates in DMEM and Ham’s F-12 medium, containing 5% fetal bovine serum and 1% penicillin-streptomycin, at 37°C under 95% O
2
/5% CO
2
. MCs were fasted in a serum-free medium for 24 h before being treated with ANG II (0.1 to 100 nM) for 5 to 60 min, or transfected with a mitochondria-targeting intracellular ANG II for 48 h (mito-ECFP/ANG II, 4 μg/well), with or without pretreatment with the AT
1
receptor blocker losartan (1 μM), AT
2
receptor blocker PD123319 (1 μM), or expression of mito-AT
2
receptors. Proteins were extracted for Western blot analysis of p-PKCα, p-ERK1/2, p38 MAPK, p65 and p50 subunits of NF-кB, or mitochondria protein complexes I to V, respectively. ANG II significantly increased p-ERK1/2 (Control: 0.20 ±0.07 vs. ANG II: 0.04 ± 0.07, p<0.05), p-PKCα (Control: 0.50 ± 0.10 vs. ANG II: 1.30 ±0.20, p<0.01), p38 MAPK (Control: 0.30 ±0.04 vs. ANG II: 0.60 ±0.06, p<0.01), and NF-кB responses (Control: 0.30 ±0.02 vs. ANG II: 0.55 ± 0.08, p<0.01) in dose- and time-dependent manners, with peak responses to ANG II occurred between 0.1 and 1.0 nM, 5-10 min (
p
<0.05). These phopho-proteomic signaling responses were attenuated by losartan (p<0.01) or PD123319 (p<0.01), respectively. mito-ECFP/ANG II increased mitochondrial protein complex I >38%, Complex III >56%, Complex IV >89%, and Complex V >63%, respectively (p<0.01). The effects of mito-ECFP/ANG II on mitochondrial protein complexes were attenuated by losartan or the expression of mito-AT
2
receptors (p<0.01). These results suggest that paracrine and intracellular ANG II may activate AT
1
and AT
2
receptors to induce important MAP kinases ERK1/2, p-PKCα, p38 MAPK, NF-кB signaling, or mitochondria responses in MCs, which may contribute to ANG II-induced glomerular injury in hypertension and kidney diseases.
Abstract P2029: Cytochrome P450 (CYP) 1B1-Estradiol Metabolite 2-Methoxyestradiol Protects Against Angiotensin II-induced Hypertension By Inhibiting CYP4A1 Expression  20-Hydroxyeicosatetraenoic Acid (20-HETE) Production In The Female Mice
Authors: Song Chi Young , Shin Ji Soo , Lew Jessica , Falck John , Malik Kafait
Published: September 2019

Previously we reported that angiotensin (Ang) II-induced hypertension is mediated by group IV cytosolic phospholipase A
2
α (cPLA
2
α) activation resulting in arachidonic acid (AA) release, and generation predominantly of eicosanoids with prohypertensive effects. Androgen dihydrotestosterone increases the expression of AA metabolizing enzyme cytochrome P450 (CYP) 4A1 and production of 20-HETE in the male rats and mice and an increase in blood pressure (BP). However, female mice that are resistant to Ang II-induced hypertension produce lower renal levels of 20-HETE, compared with males. Cyp4a12a, which has been identified as the predominant 20-HETE producing synthase in the mouse kidney, is expressed in very low levels in the female compared to male mice. Previously, we showed that the protection against Ang II-induced hypertension and associated pathogenesis in the female mice are mediated by CYP1B1-estradiol (E2) generated metabolite 2-methoxyestradiol (2-ME). These observations raised the possibility that CYP1B1-E2 metabolite 2-ME might protect against Ang II-induced hypertension by inhibiting expression of CYP4A1 and 20-HETE production. To test this hypothesis, we examined the effect of 20-HETE receptor antagonist 20-SOLA on Ang II (700 ng/kg/min, s.c. for two weeks)-induced hypertension in 8 weeks old wild type intact, ovariectomized (OVX), and intact

Cyp1b1
-/-

female mice. The systolic blood pressure (SBP, mmHg) was measured by tail-cuff. At the end of 2 weeks, Ang II caused greater increase in SBP in OVX-

Cyp1b1
+/+

(161±6) and
Cyp1b1
-/-
intact female mice (165±2) compared to the intact
Cyp1b1
+/+
mice (128±7) (p<0.05, n=4-5). 20-SOLA (10 mg/kg/day, s.c.), the 20-HETE receptor antagonist minimized Ang II-induced increase in SBP in OVX-

Cyp1b1
+/+

(116±4, Δ45) and

Cyp1b1
-/-

female mice (135±9, Δ30) (P<0.05, n= 4-5). The expression of CYP4A1 was increased in the kidney of OVX-
Cyp1b1
+/+
and intact

Cyp1b1
-/-

compared to intact

Cyp1b1
+/+

mice, which was inhibited by E2 in the former but not the later mice; however, 2-ME inhibited CYP4A1 expression in the intact

Cyp1b1
-/-

mice. These data suggest that CYP1B1-E generated metabolite 2-ME protects against Ang II-induced hypertension by inhibiting the expression of CYP4A1 and production of 20-HETE.
Abstract P2035: Severity of Hypertension Due to Elastin Haploinsufficiency is Sex-Dependent
Authors: Osei Owusu Patrick , Mohanty Ipsita , Koch Jennifer N , McCormick James A
Published: September 2019

William syndrome, an autosomal-dominant disease, is caused partly by loss-of-function mutations or gene macro-deletions resulting in elastin (
Eln
) haploinsufficiency. A major hallmark of
Eln
haploinsufficiency is hypertension, accompanied by arteriopathy and tortuous and elongated vessels. Previously, we showed that hypertension due to
Eln
haploinsufficiency in mice is due at least partly to abnormal remodeling of renal vascular signaling and increased blood pressure sensitivity to dietary salt observed only in male

Eln
+/-

mice. In this study, we tested the hypothesis that ovarian hormones protect against excessive blood pressure increase resulting from
Eln
haploinsufficiency and blood pressure sensitivity to dietary salt in female mice. We used radiotelemetry to acquire diurnal blood pressure (BP) and heart rate (HR) before and after oophorectomy (OVX) in female wild type and

Eln
+/-

mice. Four weeks after OVX, mice were placed on normal or high salt diet for 10 days, with continual acquisition of telemetry BP and HR. We assessed renal function by measuring urinary excretion of creatinine, sodium and potassium. Expression of sodium transporters was assessed by Western blot. Prior to OVX, baseline BP was elevated in

Eln
+/-

mice (WT: 114 ± 3 vs.

Eln
+/-

: 128 ± 8 mmHg;
p
=0.08). This was accompanied by a marked decrease in sodium/chloride co-transporter activity (phospho-NCC) and total-NCC in

Eln
+/-

kidneys and a trend towards increased expression of epithelial sodium channel (ENaC)-alpha and beta isoforms, and decreased trend in overnight urinary sodium excretion rate (WT: 579 ± 95 vs.

Eln
+/-

: 439 ± 82 μmol/h/g KW). Four weeks after OVX, BP was further elevated in

Eln
+/-

mice (WT: 119 ± 7 vs.

Eln
+/-

: 151 ± 10 mmHg;
p
<0.01) but was not further elevated by chronic high-salt diet (OVX + NS

Eln
+/-

: 151 ± 10 vs. OVX + HS

Eln
+/-

: 131 ± 5 mmHg;
p
=0.12). OVX also caused a robust increase in ENaC expression in

Eln
+/-

kidneys, whereas the same effect was seen in WT kidneys only after OVX plus high salt diet. We conclude that ovarian hormones suppress blood pressure elevation attributed to
Eln
haploinsufficiency and protect against blood pressure sensitivity to increased dietary sodium consumption.
Abstract P2038: A Nobel I551F Mutant of Sodium Handling Transporter NBCe1 Has Cytosolic Retention and Diminishes Transport Activity
Authors: Yamazaki Osamu , Yamashita Maho , Li Jinping , Ochiai-Honma Fumika , Yoshida Tadashi , Hirahashi Junichi , Uchida Shunya , Hayashi Matsuhiko , Shibata Shigeru
Published: September 2019

The electrogenic Na
+
/HCO
3
-
cotransporter NBCe1 is expressed in many organs and controls sodium handling. NBCe1 homozygous mutation causes not only severe hypotension but also proximal renal tubular acidosis in human and rodents. Here we shows the functional significance of the mutations reported from NCBI database on NBCe1 function. We identified 14 mutations in NBCe1 variant A(kidney type), resulting in the single amino acid substitutions, A425T, F461L, A465S, L494F, N503H, A518T, A518G, I523V, V533D, Y535H, I551F, Y554H, M753V, and L785I. Immunocytological analysis with confocal microscopy revealed only I551F mutant was expressed predominantly in the cytoplasm of HEK 293 cells and MDCK cells. Functional analysis using
Xenopus
oocytes revealed that I551F mutant had a significantly reduced activity corresponding to 52% of that of wild-type (p<0.01). Whole and biotinylated western blotting in HEK293 cells confirmed that the surface expression of I551F mutant was significantly reduced. Deglycosylation study revealed that I551F has impaired N-glycosylation. To examine the role of I551 in more detail, we also examined the properties of artificial mutants I551A, I551P, I551K, I551R, I551D and I551E in HEK293 and MDCK cells. All of artificial mutants were properly expressed in the plasma membrane. By contrast, only I551F mutant was predominantly expressed in cytoplasmic regions. These results indicate that I551F mutation inactivates the NBCe1 function with cytoplasmic retention. Because NBCe1 plays a major role in renal proximal sodium and bicarbonate reabsorption, I551F mutation may be associated with the disturbance in systemic acid-base balance or the changes in blood pressure.
Abstract P2045: Genetic Disruption of
Npr1
Depletes T Regulatory Cells and Provokes High Levels of Proinflammatory Cytokines and Fibrosis in the Kidneys of Female Mutant Mice
Authors: Gogulamudi Venkateswara R , Mani Indra , Subramanian Umadevi , Pandey Kailash N
Published: September 2019

The aim of the present study was to determine the effects of gene-knockout of guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) on immunogenic responses affecting kidney function and blood pressure (BP) in
Npr1
(coding for GC-A/NPRA) null mutant mice. We used female
Npr1
gene-disrupted (
Npr1
-/-
, 0-copy), heterozygous (
Npr1
+/-
, 1-copy), wild-type (
Npr1
+/+
, 2-copy) and gene-duplicated (
Npr1
++/++
, 4-copy) mice. Expression levels of Toll-like receptor 2/4 (TLR2/TLR4) mRNA were increased 4- to 5-fold in 1-copy mice and 6- to 10-fold in 0-copy mice; protein levels were increased 2.5- to 3-fold in 1-copy mice and 4- to 5-fold in 0-copy mice. Expression of proinflammatory cytokines and BP was significantly elevated in 1-copy and 0-copy mice compared with 2-copy and 4-copy mice. In addition, 0-copy and 1-copy mice exhibited drastic reductions in T regulatory cells (Tregs). After rapamycin treatment, Tregs were increased by 17% (
P
< 0.001) in 0-copy mice and 8% (
P
< 0.001) in 1-copy mice. Renal mRNA and protein levels of TLR2 and TLR4 were decreased by 70% in 0-copy mice and 50% in 1-copy mice. There were significantly higher levels of Tregs and very low levels of TLR2/TLR4 expression in 4-copy mice (p < 0.001). These findings indicate that the disruption of
Npr1
in female mice triggers renal immunogenic pathways, which transactivate the expression of proinflammatory cytokines and renal fibrosis with elevated BP in mutant animals. The data suggest that rapamycin treatment attenuates proinflammatory cytokine expression, dramatically increases anti-inflammatory cytokines, and substantially reduces BP and renal fibrosis in mutant animals.
Abstract P2048: Epigenetic Modification By Angiotensin II Mediates Augmentation Of Intrarenal Angiotensinogen Expression
Authors: Katsurada Akemi , Dugas Courtney M , Huisingh Nicholas R , Sato Ryosuke
Published: September 2019

Inappropriately activated intrarenal renin-angiotensin system, including proximal tubular angiotensinogen (AGT) augmentation, contributes to the progression of hypertension and associated kidney injury. It has been demonstrated that interleukin 6 (IL-6) is required for angiotensin II (Ang II)-induced AGT augmentation in renal proximal tubular cells (PTC). However, molecular mechanisms remain unelucidated. Recent studies suggest that Ang II downregulates cardiac class II histone deacetylases (HDAC), which exhibit protective effects against hypertension related tissue injury. Furthermore, HDAC9 (a class II HDAC) has been shown to act as an epigenetic repressor of proximal tubular AGT. Accordingly, the present study investigated the hypothesis that Ang II decreases HDAC9 levels, thereby enabling IL-6 to promote AGT expression in PTC. Ang II (400 ng/kg/min) was chronically perfused to male mice (N=7) for 14 days to investigate the regulation of intrarenal HDAC9. Moreover, cultured human PTC (hPTC) were used to create wild-type, HDAC9 overexpression, and HDAC9 knockdown by shRNA models and were treated with 100 nM Ang II, 10 ng/ml IL-6, or both for 24 hours. Chronic Ang II infusion elevated blood pressure and suppressed renal cortical HDAC9 levels. A decrease in HDAC9 was also observed in Ang II-treated hPTC. Treatment of hPTC with both Ang II and IL-6 increased AGT mRNA levels (1.50±0.10, ratio to the control, N=6), whereas individual treatments with Ang II or IL-6 did not alter AGT expression levels as previously demonstrated. This upregulation of AGT expression by Ang II and IL-6 co-stimulation was attenuated by the overexpression of HDAC9 in hPTC (1.10±0.08, ratio to the control). Importantly, AGT expression was enhanced by IL-6 without Ang II (2.31±0.08 by IL-6 and 2.27±0.15 by Ang II+IL-6, ratio to the control) in cells receiving the HDAC9 gene knockdown, suggesting that HDAC9 down-regulation mediates IL-6-induced AGT upregulation in hPTC. These results indicate that Ang II-induced epigenetic modification, such as the suppression of intrarenal HDAC9, results in increased accessibility of IL-6-derived transcription factors to the AGT promoter and consequent augmentation of intrarenal AGT expression in Ang II-dependent hypertension.
Abstract P2053: Blood Pressure Variability is Higher When Pulse Rate is Lower, in a Large Outpatient Database
Authors: Cahan Amos , Lerner Uri , Fishbain Barak , Bursztyn Michael
Published: September 2019

Historically, guidelines for blood pressure measurement recommended adjusting the cuff deflation rate to the patient's heart rate (2-3 mmHg per heartbeat).Current guidelines recommend a fixed cuff deflation rate of 2 mmHg/sec.. In this study, we assess the association between pulse rate (PR) and BP variability. All BP measurements in adult patients with corresponding PR documentation were reviewed in a large outpatient database. In each category (6 categories between 40 and 99 bpm), patients with at least 3 BP readings within that category were included. In each category, systolic and diastolic BP coefficient of variance (corrected for sample size) was plotted against the PR category. There were 551,595 unique patients with a total of 4,760,000 measurements, and 860,522 groups of 3 measurements or more per patient within a PR category. BP normalized coefficient of variance was inversely related to PR (Figure), ranging 0.0043 to 0.0003 (Systolic), and 0.0024 to 0.0002 (Diastolic), for the lowest to highest heart rate category, respectively. BP variability is inversely associated with PR, especially in lower PR, likely reflecting less precise BP measurements where the "sample size" of pulse is small. The observed effect compromising precision might be accompanied by a concomitant reduced accuracy of BP measurement which is another theoretical implication of a smaller "sample size", leading to a systematic bias towards measuring lower and higher than real systolic and diastolic BP respectively.
Abstract P2057: Oscar 2 & Spacelabs 90207/90217 Ambulatory Blood Pressure Monitors Differ from Each Other & Trained Clinicians Using a Mercury Column in the Laboratory
Authors: Lombardi V P , Reichhold Patrick C , Cramer Jennifer L , Harkness Hannah P , DeBell Natalie J , Dietz Nicholas R , Pate Donald L
Published: September 2019

Background & Purpose:
Our Dual Monitor Protocol with postural challenges in normotensives (n=15), hypertensives (n=14) and alcohol-dependents (n=11) revealed that an auscultatory ambulatory blood pressure monitor (ABPM) was inaccurate and unreliable, misclassifying 70% or more of hypertensives. Our goal was to apply the same procedures to determine the accuracy and reliability of oscillometric Oscar 2 and SpaceLabs 90207/90217 ABPMs.

Methods:
Two observers (O1, O2) using a mercury (Hg) column and ThinkLabs digital stethoscope assessed simultaneous, same arm BPs in 10 subjects (8 normotensives, 2 labile hypertensives) seated in the lab. ABPMs measured in triplicate simultaneous, opposite arm BPs on both arms alternating with Hg column BPs. Eight of 10 subjects were exposed to additional postural challenges in the lab, while four of 10 performed repeated 24-hr ABPM.

Results:
In the lab, the Oscar overestimated the observers’ systolic (SBP) by ~ 9 mm Hg (8.8, 95% CI: 6.9 - 10.1; 125.1 vs 116.3 mm Hg, P < 0.001), while the Spacelabs overestimated the observers’ SBP by ~ 5 mm Hg (5.4, 95% CI: 3.6 - 7.3, 121.7 vs 116.3 mm Hg, P < 0.001). Though there was a high degree of variability (both ABPMs, 15 mm Hg below to 23 mm Hg above O1O2), the average diastolic (DBP) difference was not statistically significant (Oscar vs O1O2: 69.7 vs 68.5 mm Hg, P = 0.27; Spacelabs vs O1O2: 69.9 vs 68.5 mm Hg, P = 0.23). For 24-hr ABPM in a normotensive, the Oscar had a similar average SBP (125.1 vs 125.6 mm Hg), but higher DBP (5.0 mm Hg, 67.6 vs 62.6 mm Hg, P < 0.001) and higher MAP (3.1 mm Hg, 86.7 vs 83.6 mm Hg, P < 0.001) vs observer-corrected values. For 24-hr ABPM in a hypertensive, the Spacelabs underestimated observer-corrected, 24-hr SBP, DBP and MAP by 5.2, 10.3 and 9.0 mm Hg (all P < 0.001). Both ABPMs were largely intolerant of motion, including stair climbing or walking and exhibited run-away inflations interpreted as not having exceeded SBP.

Conclusions:
While ABPMs may provide trends and predictions in population studies, we question ABPM accuracy and reliability in evaluating individual patients due to the high degree of variability. We find it unusual that approval protocols do not require postural testing. Further studies are needed to investigate the accuracy and reliability of oscillometric ABPMs.
Abstract P2059: American Medical Students Have a Higher Prevalence of Stage 2 Hypertension Than the General Public: A Cross Sectional Study
Authors: Bednarz Jacek , Mok Daniel W , Zieren Jan D , Ferguson Theresa M , Glass Jordan M , Smith Kelcie L , Yonish Brian
Published: September 2019

Relevance:
Per the National Center for Health Statistics, 7.5% of U.S. adults between 18-39 years of age have stage 2 hypertension (HTN) under 2017 ACC/AHA guidelines. Research on HTN involving American medical students is lacking. This is one of the earliest known studies to survey blood pressures and associated risk factors of American medical students.

Objective(s):
The aim of this study is to determine the prevalence of HTN in first and second year medical students and identify risk factors that could be specific to all American medical students.

Materials and Methods:
Students from The DeBusk College of Osteopathic Medicine completed a survey that queried age, gender, tobacco use, alcohol consumption, diet, aerobic exercise, mental health, social support, and past medical history. Omron BP710N sphygmomanometers were used to measure blood pressures in the left arm. Waist circumference was measured around the umbilicus. HTN stages were defined under 2017 ACC/AHA guidelines. A multinomial regression analysis was performed in SPSS v22.0 with α = 0.05 to assess risk factors for the different stages of HTN.

Results:
Of the 213 students surveyed, 49.8% (106/213) were males and 49.3% (105/213) were females. Mean age of the sample was 25.8 years and the range was between 21-37 years. Under 2017 ACC/AHA guidelines 36.6% were (78/213) were normotensive; 16.4% (35/213) had prehypertension; 29.1% (62/213) had stage 1 HTN; and 17.8% (38/213) had stage 2 HTN. The regression model was significant, χ
2
(51) = 132.003,
p
< .001, explained 51.6% (Nagelkerke R

2

) of the variance in HTN, and correctly classified 57.4% of cases. Males were 13.26 times more likely (p<0.001) to develop prehypertension than women. Increasing waist circumference by 1 inch was associated with an 11% increase in developing stage 2 HTN (p<0.001).

Conclusion:
Medical students have a ~2.4 times higher prevalence of stage 2 HTN than the public. Anxiety, exercise, and diet were insignificant factors according to the regression model while gender, waist circumference, and amount of sleep were significant. Additional studies should be conducted to assess the prevalence of stage 2 HTN and develop a better understanding of what risk factors may be causing the increased prevalence of stage 2 HTN in medical students.
Abstract P2061: Cardiovascular Risk Profile of a Young Adult Population Assisted by a Family Healthcare Unit in Rio De Janeiro With High Risk for Obstructive Sleep Apnea Screened By Stop-Bang Questionnaire and Epworth Sleepiness Scale
Authors: Azevedo Rafael B , Andrade Letícia Z , Ferreira Leonardo V , Silva Rodrigo , Hollanda João Victor G , Sampaio Fernando B , Castro Raquel E , Oei Stephanie S , Rego Maria Fernanda d , Muxfeldt Elizabeth S
Published: September 2019

Objective:
To establish the relationship between cardiovascular (CV) risk profile and detected risk of Obstructive Sleep Apnea (OSA) in two questionnaires - STOP-BANG (SB) and Epworth Sleepiness Scale (ESS), in a young population of adults registered in a Family Health Unit (USF) located in Rio de Janeiro, Brazil - LapARC cohort study.

Methods:
This cross-sectional population study enrolled adults between 20-50 years old, registered in a primary healthcare unit in Rio de Janeiro. A database is being developed including sociodemographic and anthropometric data, and CV risk factors. Office blood pressure (OBP) and Home Blood Pressure Monitoring (HBPM) (7-day protocol) were obtained with Omron-705CP. Furthermore, OSA was investigated by SB and ESS. Patients with a high risk for OSA in either of these two questionnaires were subsequently assigned for polysomnography (PSG).

Results:
A total of 391 subjects were evaluated [40% males, 38 ± 8 years], where 96 (25%) were identified as high risk for OSA by the SB questionnaire and 143 (37%) by ESS. The most common CV risk factor was physical inactivity (45%), followed by dyslipidemia (34%) and obesity (24%). By OBP, the prevalence of hypertension was 24% while by HBPM was 18%, with a low concordance between them (kappa=0.385). Subjects with a high risk by SB are older, with a higher prevalence of obesity (50% vs 16%), hypertension (29% vs 9%), and higher office BP and HBPM. On the other hand, individuals with high-risk by ESS were more obese (34% vs 19%), with increased waist circumference (48% vs 32%), higher prevalence of dyslipidemia (43% vs 41%) and metabolic syndrome (13% vs 7%). However, there was no difference in BP levels. Among the subjects assigned to PSG, 46% had a diagnosis of OSA (AHI ≥ 5/hour) and 23% of moderate/severe OSA (AHI>15/hour). The best predictor of OSA was SB, positive in 100% of subjects with moderate/severe OSA, while ESS was positive in only 20% of them.

Conclusion:
This young and apparently healthy population presented a high prevalence and risk for OSA. The SB had a higher association with higher BP levels, while ESS was associated with a worse metabolic profile. Therefore, SB questionnaire seems to be the best predictor for moderate/severe OSA in this population.
Abstract P2064: Changes in Inflammatory Markers Monitored Across Time After Bariatric Surgery in Severely Obese Patients
Authors: Oliveras Anna , Benito David , Vázquez Susana , Vera Maria , Outon Sara , Goday Albert , Sans Laia , Pascual Julio , Riera Marta
Published: September 2019

Adipose tissue is a higly active endocrine tissue and produce adipokines, peptides produced by adipose tissue and exerting autocrine, paracrine and endocrine function.

Objective:
to analyze changes (Δ) in serum levels of several adipokines and inflammatory markers in morbidly obese patients (MO) after bariatric surgery (BS) at several follow-up time points.

Methods:
Fifty-two MO (81% women, 40% hypertensives, age 43.9±8.9 yr, BMI 42.2±5.4 Kg/m
2
, waist circumference 131.6±12.1 cm) were evaluated prospectively before and 1,3,6 and 12 months (m) after BS, with assessment of anthropometric data and serum concentrations of several adipokines and inflammatory markers. BS technique: laparoscopic gastric by-pass (28 of 52) and sleeve gastrectomy (24 of 52).

Results:
at 12m body weight (-35.7±10.2 Kg) and waist circumference (-27.2±9.4 cm) decreased (p<0.001). Two inflammatory markers, leptin and hsCRP, decreased at 1,3,6 and 12m (p<0,005 for all). Adiponectin and angiopoetin-2 increased from month 3 on. (Table). These Δ were statistically significant when examined by an ANOVA with repeated measures, excepte for adiponectin (p=0.065). After adjusting for age, sex, and BS technique, the BS technique was statistically significant only for ΔhsCRP (p=0.035). Pearson correlations were explored. There were no statistically significant correlation between Δ body weight or Δ waist circumference with changes of any of these markers at any follow-up time point.

Conclusions:
there is a decrease in inflammatory markers 1 m after BS in MO patients with progressive decrease throughout 12 m. These changes are independent of the BS technique and of Δ in body weight and waist circumference.
Abstract P2071: β-1,3/1,6-d-glucan Of Indonesian
Ganoderma Lucidum
Mycelium Extract Reduces Systolic Blood Pressure & Inflammation In Hypertensive Patients
Authors: Sugita Peter , Fadlan MR , Sargowo Djanggan , Rizal A
Published: September 2019

Background:
Extract of
Ganoderma
lucidum
Mycelium containing β-1,3/1,6-D-Glucan has shown to possess beneficial effects on cardiovascular diseases.

Objective:
To examine the effectiveness of β-1,3/1,6-D-Glucan (GLME) consumption to reduced blood pressure (BP) & inflammation in patients with hypertension.

Material and Methods:
A randomized, double-blind, placebo-controlled clinical trial was conducted in 50 hypertensive adults (JNC VII, age 50-70 years). The patients were divided into 6 groups. Group A: received GLME 540mg/day + CCB, Group B: GLME + ACEI/ARB, Group C: placebo + ACEI, Group D: placebo + CCB, Group E: GLME only & Group F: placebo only. We used the Morisky score to evaluate treatment’s adherence & excludes patients with Morisky < 6. A standardized method was used to measure BP at baseline and thereafter every 30 days until day 90. Further, heart rate (HR), LVEF, LVMI, hsCRP, MDA, TNF-α, IL-1, & IL-6 were measured at baseline & at 90-days.

Results:
At day 90, GLME lowered systolic BP (SBP) compared to placebo (–22.82±11.4 vs. –10±16.0 mmHg; p= 0.007), DBP was lowered without significant difference between GLME & placebo groups. The change in mean arterial pressure was significance compared with placebo p= 0.028. Group B have the most reducing SBP effect compared with others, p=0.000. The reducing effect of mean arterial pressure was significance in group A compared with others, p= 0.008. In Group B, we found that there was a significance decreasing in hsCRP compared with p=0.01. The reducing effect LVMI, TNF-α, plasma IL- 6 and IL-1 concentration was significantly lower in group B compared with other group (p= 0.043, p= 0.001, p= 0.0008, p= 0.0005, respectively).

Conclusion:
GLME may significantly reduce SBP systolic & LVMI & may have an anti-inflammatory effect shown through the reduction of IL-6, IL-1β, and TNF-α.
Abstract P2073: Blood Pressure Measurement: Should Technique Define Targets?
Authors: Ruzicka Marcel , Hiremath Swapnil
Published: September 2019

Background:
Advancements in technology over the last decades have brought a mini-revolution into the centuries old technique of blood pressure (BP) assessment. Automated oscillometric BP devices allow not only to eliminate human error in BP readings, but more importantly they standardize the length of resting period and allow for unattended resting and BP measurement. BP thresholds for definition of hypertension as well as BP treatment targets are however largely derived from studies using mercury sphygmomanometers or non-automated oscillometric BP devices. Comparative studies addressing the effect of standardized length of unattended resting and presence versus absence of medical personnel during BP measurement per se are however lacking.

Methods and Population:
In this prospective randomized, crossover trial we compared office casual BP readings to BP readings after 5 minutes unattended resting and unattended BP measurement. Additionally, we compared 5 minutes unattended resting and unattended BP measurement with medical personnel presence during BP measurement. BP readings were obtained from the same arm on 2 different visits using an automated oscillometric BP device (Omron HEM 907XL), one pre- and second one post 24-hour ABPM. All patients followed at our regional, tertiary care hospital-based Hypertension Centre were eligible for this trial.

Results:
90 adult patients were consented and 79 (men 54% and women 46%) completed all the measurements. Mean casual BP was 137. 1 ± 16.7, mean resting unattended BP was 130.1 ± 13.7, indicating difference of 7.0 + 10.0 mm Hg (p < 0.0001). Mean resting attended BP was 129.3 ± 13.2 (not statistically different from completely unattended resting BP, difference - 2.7 [95% CI 1.4 -6.8] p = 0.18).
Summary:
Our study conclusively confirms that resting decreases blood pressure as assess from the difference between casual BP and BP obtained after 5 minutes of rest. More importantly, our study indicates that presence of medical personnel during BP measurements after initial 5 minutes unattended rest does not have a significant impact on overall resting BP readings.

Conclusion:
These data no superiority of fully automated devices versus semi-automated devices for BP measurements