bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P3006: Angiotensin-(1-7) Prevents Doxorubicin-Induced Aortic Dysfunction Through Anti-Fibrotic Mechanisms in Juvenile Male and Female Sprague Dawley Rats
Authors: Tallant E. Ann , Rahimi Omeed , Varagic Jasmina , Westwood Brian M , Gallagher Patricia E
Published: September 2019

Doxorubicin (Dox) is an effective, anthracycline chemotherapeutic administered for a variety of malignancies, but clinical use of the drug is limited by a cumulative, dose-dependent cardiotoxicity. Thus, adjuvant therapies are needed to mitigate Dox-induced cardiovascular damage in cancer patients, especially in pediatric patients with decades of life ahead. Our group showed that angiotensin-(1-7) [Ang-(1-7)], an endogenous peptide hormone with anti-cancer properties, improved vascular dysfunction in coronary vessels and cremaster muscle microvessels in Ang II-infused rats. In this study, juvenile male and female Sprague Dawley rats (n = 8-10) were administered a clinically equivalent dose of Dox (21-24 mg/kg) over 6 weeks, in the presence or absence of Ang-(1-7) [24 μg/kg/h]. Aortic function was measured using echocardiography. In both sexes, Ang-(1-7) blocked the Dox-mediated increase in pulse wave velocity (PWV), a measure of arterial stiffness (75% in males and 179% in females, p<0.05 and p<0.001). Dox decreased aortic lumen diameter (by 18%, p<0.01) and increased wall thickness at systole (p<0.01) in males, which was attenuated by Ang-(1-7). In male but not female aortas, Dox increased media hypertrophy by 16% (p<0.01) and reduced elastin content by 17% compared to control rats (p<0.001), changes prevented by Ang-(1-7). Conversely, collagen deposition was increased 2.5-fold in the aortic arches of female rats treated with Dox (p<0.001), which was blocked by Ang-(1-7). Dox increased nuclear ERK1/2 by 2-fold in the aortic media of male rats (p<0.01) and Ang-(1-7) significantly attenuated nuclear ERK1/2 localization. In contrast, neither Dox nor Ang-(1-7) changed total or nuclear ERK1/2 in the aortic arches of female rats. Dox increased nuclear pSMAD2 4-fold in males (p<0.05) and 3-fold in females (p<0.05); prophylactic treatment with Ang-(1-7) reduced the Dox-induced increases in nuclear pSMAD2 while the heptapeptide hormone had no effect alone. These results demonstrate that Ang-(1-7) prevented Dox-induced aortic dysfunction in both sexes, albeit through different mechanisms, suggesting that treatment with Ang-(1-7) may serve as an effective adjuvant to improve Dox-induced vascular dysfunction in pediatric patients.
Abstract P3007: Effect of Anti-Hypertensive Treatment Lisinopril on Central Arterial Stiffness and Anxiety-Like Behavior in Adult Hypertensive Dahl Salt-Sensitive Rats
Authors: Fenner Rachel C , Grigorova Yulia , McDevitt Ross , Petrashevskaya Natalia , Wei Wen , Lakatta Edward , Fedorova Olga , Ajamu Samuel
Published: September 2019

Background:
Independent of a high salt intake, Dahl Salt-Sensitive (DSS) rats demonstrate an age-associated increase in blood pressure (BP), and central arterial stiffness estimated by pulse wave velocity (PWV) accompanied by cognitive decline. We hypothesized, that anti-hypertensive treatment Lisinopril, in addition to BP decrease, will lower PWV and improve cognition of adult DSS.

Methods:
Twenty 6-mo old male DSS were kept on normal salt diet for the duration of the study; ten of them were continuously treated with Lisinopril (15 mg/kg/day) for 3 months. Systolic BP (SBP) and PWV (by doppler echocardiography) were measured, and open field test (OFT) was performed to assess locomotor and anxiety-like behavior at baseline prior to treatment and repeated in 3 months in 9-mo old rats. In a sub-cohort of DSS rats SBP was measured in 3-mo-old DSS. The data are presented as mean ± standard deviation and analyzed by 2-way ANOVA and T-test.

Results:
Prior to treatment, all DSS rats displayed hypertension and BP elevation with age (SBP: 170±11 vs. 142±5 mmHg, 6-mo vs. 3-mo; P<0.01). After 3 months, control untreated animals showed no difference in SBP and were hypertensive. Rats treated with Lisinopril for 3 months showed a decreased SBP (119±9 vs. 171±11 mmHg, P<0.0001) and a decreased PWV compared to their baseline prior to treatment (3.03±1.23 vs. 5.52±1.07 m/s p<0.05). In OFT, treatment with Lisinopril increased exploration of the center of the field compared to the control group (120±35 vs. 87±30% of distance traveled in center to baseline , p=0.05) without affecting total distance traveled, indicating a reduction in anxiety-like behavior.

Conclusion:
Lowering of BP and PWV is associated with reduced anxiety-like behavior in DSS, which indicate the connection of cardiovascular disorder and cognitive function in adult hypertensive DSS. Whether Lisinopril has an additional direct effect on brain structure and function in DSS rats will be further studied. This research was supported entirely by the Intramural research Program of the NIH, National institute on Aging
Abstract P3008: Beta Adrenergic Receptor Activation Causes Endothelial Glycocalyx Degradation
Authors: Jackson-weaver Olan , Friedman Jessica , Hoof Marcus , Drury Robert , Packer Jacob , Guidry Chrissy , Duchesne Juan , Rodriguez Laura
Published: September 2019

The endothelial glycocalyx is a proteoglycan and glycoprotein matrix that coats the luminal surface of endothelial cells. It is an important component of the permeability barrier function of endothelial cells, including in the glomerular capillaries. Furthermore, it is a sensor of shear stress, and in vessels treated with enzymes to remove the glycocalyx do not exhibit flow-mediated vasodilation. Sparse previous studies have implicated a reduced glycocalyx thickness in hypertensive patients, but the causative signaling mechanisms have not been investigated. We and others have found that the endothelial glycocalyx can be studied in cultured endothelial cells if the medium contains significant soluble protein. We hypothesized that elevated catecholamines cause shedding of the endothelial glycocalyx
in vitro
. We cultured human umbilical vein endothelial cells (HUVECs) in M200 medium supplemented with 1% bovine serum albumin to permit development of a glycocalyx. We exposed these cells to concentrations of epinephrine, norepinephrine, phenylephrine, or isoproterenol from 0.01 to 10 μM for 30 minutes. We then imaged the glycocalyx using fluorescently labelled wheat germ agglutinin. We found that norepinephrine, epinephrine, and isoproterenol all caused a significant decrease in the endothelial glycocalyx staining intensity (5.82 ± 0.28 vs. 4.82 ± 0.21, 6.82 ± 0.28 vs. 5.09 ± 0.25, 7.46 ± 0.33 vs. 6.51 ± 0.28, at 1 μM, 1 μM, and 0.1 μM, respectively). However, phenylephrine caused an increase in glycocalyx staining intensity (6.27 ± 0.25 vs. 7.72 ± 0.32 at 1 μM). These results suggest that catecholamines acutely cause degradation of the glycocalyx in endothelial cells, but only when β adrenergic receptors are involved, since phenylephrine actually acted to increase glycocalyx. Future work will be needed to investigate the pathophysiological role of the reduced glycocalyx in hypertension. Furthermore,
in vivo
experiments are needed to determine whether these results are applicable to endothelial cells in the complex environment of intact blood vessels. Future work will also investigate the signaling mechanisms leading from adrenergic receptor activation to enzymatic degradation of the glycocalyx.
Abstract P3011: Role of CD36 in Insulin Mediated Microvascular Vasodilation in African Americans
Authors: Shibao Cyndya A , Abumrad Nada A , Abumrad Naji N , Parsa Dena , Celedonio Jorge E , Scudder Shea K , Breier Nicholas C
Published: September 2019

CD36 is a membrane protein involved in fatty acids uptake that is expressed in the endothelium, which has been associated with endothelial dysfunction in African Americans (AA). One in four AA is G-allele carriers for coding CD36 SNP rs3211938, which results in ~50% reduction in its expression. We reported that potentiating nitric oxide action (NO) with sildenafil restored endothelial dysfunction in conduit arteries in G-allele carriers. In this study, we tested the hypothesis that in G-allele carriers, sildenafil would improve insulin-induced microvascular recruitment (MBV) in response to fat infusion. We recruited 25 healthy AA (17 non-carriers [ages 34 ± 7.4] and eight G-allele carriers [42 ± 7.4 yrs]). Subjects underwent three visits: Visit 1: Saline infusion and hyperinsulinemic euglycemic clamp (HIE clamp). Visit 2: Lipid infusion and HIE clamp and Visit 3: Lipid infusion and HIE clamp after a four-week sildenafil treatment (60 mg/day). During each visit, the subjects underwent an assessment of MBV at baseline (bsl), after 3-hour insulin (Ins) infusion (40mu/m
2
/min) and after Ins and L-arginine (10mg/kg/min) for 30 min. infusion (Ins+L-arg). Ins+L-arg (saline day) increased the % change in MBV in both groups. However, this increase was less in carriers as compared to non-carriers (13.6±42.4 and 38.9±74.4),
Fig. A.
Intralipid (IL) infusion increased MBV but only in non-carriers,
Fig. B
. Treatment with sildenafil in the presence of IL infusion induced a decline in MBV in G-allele carriers
Fig. C
. In conclusion, healthy AAs with CD36 deficiency had a poor insulin-induced microvascular recruitment and appeared to be worsened by potentiating NO function with sildenafil.
Abstract P3013: Infusion of Recombinant Human Thioredoxin-1 Completely Protects Against High Fat-Induced Endothelial Dysfunction in Small Mesenteric Arteries From Male C57bl6/j Mice
Authors: Hilgers Rob H
Published: September 2019

Background:
Obesity is a serious risk factor for cardiovascular diseases. A high fat diet results in cellular oxidative stress and endothelial dysfunction in resistance-sized arteries, characterized by reduced nitric oxide (NO) and endothelium-dependent hyperpolarizing (EDH) responses. Thioredoxin-1, an oxidoreductase protein that cleaves disulfide bridges between two adjacent cysteine residues in oxidized proteins, has been shown to lower blood pressure and improve endothelium-dependent relaxing responses in aged C57Bl6/J mice.

Methods and Results:
Young (~ 3 month-old) male C57Bl6/J mice were fed a high fat diet (42% kcal from fat) or a normal chow. Mice were administered recombinant human thioredoxin-1 (rhTrx1; 1 mg/mL) or saline (0.9% NaCl) via tail vein injection at the start, one- and two months after diet regimen. Body weight (BW) was comparable between lean/rhTrx1 and lean/saline at the time of euthanasia (32 ±1 g versus 32 ± 1 g). The high fat regimen resulted in a comparable BW between obese/saline and obese/rhTrx1 mice (47 ± 1 g versus 45 ± 2 g, respectively). After three months, mice were euthanized and small (second-order branches of the superior) mesenteric arteries were isolated and mounted on the wire-myograph to assess vascular reactivity. Small mesenteric arteries from obese/saline had blunted acetylcholine (10
-9
- 10
-5
M)-mediated relaxations compared to lean/saline mice (pEC
50
5.29 ± 0.27 versus 6.61 ± 0.15, respectively). In obese/rhTrx1 mice, these responses were not statistically significantly different from lean/rhtrx1 mice (pEC
50
6.66 ± 0.25 versus 6.59 ± 0.31, respectively). There were no differences in the sensitivity to the NO donor sodium nitroprusside between the four experimental groups. EDH relaxing responses to the K
Ca
3.1 channel opener NS309 (10
-9
- 10
-5.5
M) were blunted in obese/saline compared to lean/saline (pEC
50
6.37 ± 0.12 versus 6.83 ± 0.08). In obese/rhTrx1 mice, these responses were not statistically significantly different from lean/rhTrx1 mice (pEC
50
7.07 ± 0.13 versus 6.63 ± 0.16, respectively).

Conclusion:
Infusions with rhTrx-1 prevents endothelial dysfunction in obese mice by improving the EDH response.
Abstract P3021: Trimethylamine but Not Trimethylamine N-Oxide Increases Blood Pressure in Rats, Affects Viability of Vascular Smooth Muscle Cells and Degrades Protein Structure
Authors: Konop Marek , Jaworska Kinga , Bielinska Klaudia , Bielak-Zmijewska Anna , Mosieniak Grazyna , Sikora Ewa , Pilz Marta , Derzsi Ladislav , Sozanski Krzysztof , Holyst Robert , Ufnal Marcin
Published: September 2019

Increased plasma level of trimethylamine N-oxide (TMAO), a liver metabolite of gut bacteria-produced trimethylamine (TMA), has been suggested to increase cardiovascular risk. Mechanisms of TMAO increase in plasma and biological effects of TMAO are obscure. We evaluated the impact of heart failure (HF) on plasma levels of TMA and TMAO, and biological effects of the molecules.

Gut permeability was evaluated in male, 58-week-old Spontaneously Hypertensive Heart Failure (SHHF) and Wistar-Kyoto (WKY) rats. TMA and TMAO levels were assessed using LC-MS. Mean arterial blood pressure (MABP) was measured in anaesthetized, male, 16-week-old WKY treated intravenously with either 0.9% NaCl (vehicle), TMA or TMAO. The cytotoxicity of TMA and TMAO in human vascular smooth muscle cells (hVSMCs) was evaluated using MTT assay. The effect of TMA and TMAO on protein structure of bovine albumin was assessed by fluorescence correlation spectroscopy.

WKY showed no pathological changes in the circulatory system. SHHF showed HF with reduced ejection fraction. In comparison to WKY, SHHF had a significantly higher plasma level (μM) of TMA (99.05±6.40 vs 149.30±21.87) and TMAO (5.22±0.61 vs 6.69±0.67). SHHF had a significantly higher plasma-to-stool ratio of TMA, decreased intestinal blood flow and morphological alterations in the colon indicating the increased gut-to-blood penetration of TMA due to HF-induced leaky gut.

In WKY treatment with the vehicle and TMAO did not affect MABP. In contrast, TMA (at equimolar doses to TMAO) significantly increased MABP by 5-40 mmHg in a dose dependent manner. In vitro, TMA at a concentration of 500μM reduced hVSMCs viability. TMAO at a concentration of 100mM was not cytotoxic whereas TMA at the same concentration killed cells within 24h. Finally, the incubation of albumin with TMA but not with TMAO resulted in the degradation of the protein structure.

In conclusion, HF rats show increased plasma TMA and TMAO, which results from increased gut-to-blood penetration of TMA, a TMAO precursor. TMA but not TMAO affects hemodynamics in rats, reduces viability of cells and degrades protein structure. Therefore, TMA but not TMAO may exert deleterious effects on the circulatory system. Further clinical studies should evaluate not only TMAO but also TMA.
Abstract P3022: Pentoxifylline Exerts Antiinflammatory And Antioxidant Effects, Inhibits MMP-2 Activity And Attenuates Renovascular Hypertension-Induced Vascular Alterations
Authors: Rizzi Sanchez Elen , Bonacio Gisele , Batista Rose Ines Matos , Garcia Vitoria Tomazelli , Gonçalves Bruna R , Victorino Thais R , Dellalibera-Jovilliano Renata , Franca Suzelei C , Tanus-Santos Jose E
Published: September 2019

Introduction:
Angiotensin II promotes inflammation, oxidative stress and matrix metalloproteinases (MMP) activation leading to vascular remodeling in hypertension. Pentoxifylline (PTX) is a non-selective inhibitor of phosphodiesterases that has also shown antiinflamatory and antioxidant effects. Thus, the aim of the present study was to evaluate whether PTX treatment decreases morphological and functional vascular alterations in 2-kidney and 1-Clip (2K1C) rats through reduction of cytokines, oxidative stress and MMP-2 activity.

Methods:
Male 2K1C and Sham rats were treated with Vehicle or PTX. Systolic blood pressure (SBP) was measured weekly. Aortic rings were isolated to assess endothelium-dependent relaxations. The vascular hypertrohy were examined in the aorta sections stained with hematoxylin/eosin. Aortic MMP-2 levels and gelatinolytic activity were determined using gelatin and
in situ
zymography assays, respectively. Vascular oxidative stress was evaluated using dihydroethidium (DHE). Cytokines levels were analyzed using the enzyme-linked immunosorbent assay (ELISA).

Results:
2K1C rats exhibited high SBP (195±4 mmHg vs Sham 123±2 mmHg ) and significant vascular hypertrophy when compared to Sham group (0.7±0.03 mm
2
vs
0.5±0.02 mm
2
; p<0.05), which were attenuated with PTX treatment (174±4 mmHg and 0.6±0.02 mm
2
;p<0.05). PTX treatment also ameliorated the endothelial dysfunction in aortas from 2K1C rats (from 78±5% to 98±6%; p<0.05). MMP-2 levels and activity were augmented in 2K1C rats when compared to sham group (p<0.05). The treatment with PTX reduced MMP-2 upregulation in 2K1C rats (p<0.05). Overproduction of ROS in aortas from 2K1C rats (136±1.8%) was reduced with PTX treatment (21±8%; p<0.05). Elevated tumor necrosis factor-alpha and interleukin-1 beta levels in 2K1C rats was diminished with PTX treatment (p<0.05).

Conclusion:
PTX ameliorates 2K1C-induced hypertension, vascular morphometric and functional alterations, oxidative stress, elevated MMP-2 activity and cytokines levels. PTX exerted antioxidant and immunomodulatory effects, and decreased renovascular hypertension-induced MMP-2 up-regulation, leading to improvement of vascular dysfunction and remodelling typically found in 2K1C hypertension.
Abstract P3024: Tangential Wall Stress In The Thoracic Aorta Affects The Structure And Function Of Associated Perivascular Adipose Tissue
Authors: Contreras Andres , Watts Stephanie W , Lauver Adam , Garver Hannah , Fink Gregory D
Published: September 2019

Perivascular adipose tissue (PVAT) dynamically modifies contractile function of the blood vessel it surrounds (outside-in signaling). Sparse evidence points to inside-out signaling, i.e. the blood vessel actively affecting its surrounding PVAT. We hypothesized that inside-out signaling to PVAT could occur in response to changes in tangential vascular wall stress. We created a coarctation of the thoracic aorta in male Sprague-Dawley rats to chronically expose PVAT to higher (above) and lower (below) pressures (and thus wall stresses). This allows comparison of PVAT from the same animal to different vascular pressures with confounding factors (neurohormonal environment) presumably being equal. In some animals, dual-channel pressure telemeters were used to simultaneously measure arterial pressure in the aorta of conscious rats above and below the coarctation. Post-surgery (4-8 weeks), thoracic aortic samples + PVAT were dissected above and below coarctation to determine elastin and collagen content of PVAT. Functionally, the adipogenic capacity of PVAT preadipocytes, PVAT-assisted stress relaxation and contraction to phenylephrine (PE) were compared. Telemetry revealed a ~22 mmHg systolic pressure gradient across the coarctation. Collagen deposition (picrosirius red) in PVAT above coarctation increased by 92% vs below (above=1.13±0.23% vs below=0.65±0.23% of PVAT area, n=4, P<0.05); elastin content did not change. Differentiated adipocytes derived from the PVAT above the coarctation accumulated 31% less triglycerides vs those below, and vs retroperitoneal adipose tissue [below=1 (set), above=0.69±0.1%, retroperitoneal=4.15±0.1%, n=4 P<0.05]. Finally, the ability of PVAT to assist stress relaxation (greater relaxation in +PVAT vs -PVAT) over a 6 gram tension range was reduced ~50% (N=5) in PVAT above vs below the coarctation; the anti-contractile function of PVAT in PE-induced contraction did not differ above vs below. In summary, PVAT of thoracic aorta under different distending pressures/wall stress exhibit significantly different structural and functional properties. These data support the hypothesis that signaling (factors derived) from the vascular wall influences the function of its PVAT.
Abstract P3027: Response to Exercise Dictates Metabolic and Microbiotal Effects of a High-Salt Diet With Aging
Authors: Koch Lauren G , Zhang Youjie , Spegele Adam C , Doty Tyler , Mell Blair , Cheng Xi , Yeo Ji-Youn , Joe Bina
Published: September 2019

Individual variation in response to exercise could be critical to sustaining cardiorespiratory fitness with aging. In order to explore this idea, we developed preclinical animal models of low and high response trainer rats (LRT and HRT, respectively) by selective breeding based on change (Δ) in performance on a maximal treadmill running test after an 8-week standardized aerobic training program. To test the hypothesis that individuals with low adaptive capacity to exercise training (like LRT rats) are more vulnerable to the development of hypertension associated with aging compared to individuals with high adaptive ability (like HRT rats), we subjected 24-month old male rats to a high-salt diet (HSD, 2% NaCl) for 32 days and evaluated cardiovascular and metabolic responses. We observed no significant change in resting blood pressure (telemetry implants, DSI) after HSD suggesting neither strain is salt-sensitive (LRT vs. HRT before HSD, 115.9 vs. 120.8; after HSD, 112.4 vs. 118.4 mmHg). However, resting heart rate decreased in both strains in response to HSD (ΔLRT = -32.2 bpm and ΔHRT = -30.9 bpm). Metabolic evaluation (CLAMS, Columbus Instruments) showed LRT rats significantly decreased food intake (ΔLRT vs. ΔHRT, -9.64 vs. 3.86 g/kg/day; P < 0.01) and water consumption (ΔLRT vs. ΔHRT, -11.8 vs. 7.5 ml/kg/day; P < 0.05) after HSD compared to HRT. Interestingly, we found that the respiratory exchange ratio (RER) was significantly lowered in LRT rats (before HSD, 0.95; after HSD, 0.90; P < 0.05), but a trend of increasing RER occurred in HRT rats after HSD. Accordingly, we observed opposite and inverse trends in fat and glucose oxidation indicating that aged LRT and HRT rats reprioritize energy metabolism differently in response to HSD. Both strains maintained their normal body weight and plasma concentration of sodium while coping with HSD. In addition, 16S rRNA profiling of fecal samples revealed that the relative abundance of several gut bacteria including
Lactobacillaceae
and
Turicibacteraceae
increased in LRT rats (ΔLRT, 5.6% and 4.6% respectively) but not in HRT rats. Together, these data suggest that rats bred for their ability to respond to exercise adapt differently to a HSD in order to maintain cardiovascular and metabolic homeostasis.
Abstract P3029: A Randomized Controlled Trial Evaluating a Novel Just-In-Time Contextual Mobile Application Intervention to Reduce Sodium Intake in Hypertension: The Lowsalt4life Trial
Authors: Dorsch Michael P , Cornellier Maria L , Poggi Armella D , Bilgen Feriha , Chen Peiyu , Wu Cindy , An Lawrence C , Hummel Scott L
Published: September 2019

Introduction:
Interventions that lower sodium intake can decrease blood pressure and improve cardiovascular outcomes.

Methods:
This single center, prospective, open-label study evaluated a new mobile app to reduce sodium intake. Patients > 18 years of age diagnosed with hypertension and on antihypertensive therapy for at least 3 months were enrolled. Participants were randomized 1:1, stratified by gender, to receive the mobile app, or usual dietary advice for 8 weeks. The app provides a multifaceted intervention based on just-in-time contextual tailored messages. The primary endpoint was the change in 24-hour urinary sodium excretion. Secondary outcomes included the change in estimated sodium intake from a Block Food Frequency Questionnaire (FFQ), 24-hr dietary recall, Self-care Confidence in Following a Low-Sodium Diet (SCFLSD) survey and blood pressure (BP).

Results:
Fifty patients (24 App, 26 No App) were randomized. Baseline demographics were similar between the groups. The average age was 57 years and BP 131/83 mmHg. The reduction in 24-hour urinary sodium excretion from baseline was greater in the App compared to No App group (p=0.30). The reduction in FFQ (p=0.008) and 24-hr dietary recall (p=0.11) sodium intake from baseline were greater in the App compared to No App group. Systolic BP was reduced from baseline in the App compared to No App group (-7.5 vs. -0.7 mmHg, p=0.12). No significant change was shown in the SCFLSD survey.

Conclusions:
Patients randomized to the app had a greater reduction in measures of sodium intake and systolic BP from baseline to 8 weeks compared to those that did not receive the application. Further studies are needed to confirm these results.
Abstract P3033: Sodium Induced Dopamine D1 Receptor (D1R) Plasma Membrane Recruitment Involves Protein Phosphatase 2a (PP2A) and Aminopeptidase N (APN)
Authors: Mallory Micah J , Xu Peng , Schiermeyer Katherine A , Gildea John J , Felder Robin A
Published: September 2019

The cooperative relationship between the dopamine type 1 receptor (D
1
R) and the angiotensin type 2 receptor (AT
2
R) signaling pathway in renal proximal tubule cells (RPTCs) is known as a significant mediator of natriuresis and systemic sodium (Na
+
) homeostasis. The degree of Na+ induced D
1
R plasma membrane recruitment correlates with the degree of salt sensitivity of blood pressure in urine-derived RPTCs collected from clinical study participants. We recently published that the Protein Phosphatase 2A (PP2A) pathway is a common and necessary pathway for D
1
R and AT
2
R cooperativity and function. Here, we extend these studies by examining the autocrine signaling in previously published model RPTCs that are normally D
1
R cAMP coupled (i22) and D
1
R cAMP uncoupled (i19). D
1
R and aminopeptidase N (APN) plasma membrane expression was measured by flow cytometry, and an elevated NaCl solution (PBS + 50 mM NaCl, 1 hour) was used for increased salt exposure. The addition of FTY720 (2.5 μM, 1 hour) activated PP2A. Normally coupled i22 cells in the presence of increased Na
+
significantly increase plasma membrane D
1
R (1.41±0.10 fold vs VEH, n=3 p<0.05), but uncoupled i19 cells did not. FTY720 alone did not significantly increase plasma membrane D
1
R in uncoupled i19 cells; however, FTY720 along with increased Na
+
did significantly increase i19 plasma membrane D
1
R (1.61±0.17 fold vs VEH, n=9 p<0.001). In order to inhibit local production of dopamine, BCH (2-aminobicyclo(2,2,1)-heptane2-carboxylic acid, 1 mM), a LAT2 inhibitor, and Carbidopa (100 μM), a dopamine decarboxylase inhibitor, were used and completely blocked the plasma membrane recruitment of D
1
R. We next looked at enzymes involved in the regulation of AngIII peptide, the preferred agonist of the AT
2
R. APN is the enzyme that converts AngIII to AngIV. Under elevated Na
+
conditions levels of APN significantly decreased in normally coupled i22 but not in the uncoupled i19 cells (-7.3 ±0.01% vs VEH, n=6 p<0.01). In summary, the data presented suggests that PP2A and enzymes involved in the local production of dopamine and AngIII, may be involved in the Na+ induced plasma membrane recruitment of D
1
R.
Abstract P3034: Female Mice are Protected Against Renal Inflammation and Salt-Sensitive Hypertension During Diabetes
Authors: Shen Justin Z , Hernandez Adela , Bernstein Ellen A , Veiras Luciana C , Khan Zakir , Cao DuoYao , McDonough Alicia A , Bernstein Kenneth E , Giani Jorge F
Published: September 2019

Introduction:
Diabetic nephropathy is characterized by renal inflammation and impaired kidney function that predisposes to salt-sensitive hypertension. However, the prevalence of diabetic kidney disease is lower in females compared to males. Here, we aim to study the sexual differences associated with the progression of diabetic nephropathy and the response to a high salt diet.

Methods:
Four- and seven-month old male and female diabetic (db/db) and non-diabetic (db/+) mice received either a high-salt (4% NaCl w/w) or a control (0.4% NaCl w/w) diet for four weeks (n=4). Mean arterial pressure (MAP) was measured by telemetry. To evaluate sodium handling, mice were challenged with an intraperitoneal injection of saline solution (0.9% NaCl) in a volume equivalent to 10% of the mouse body weight and hourly sodium excretion was evaluated by flame photometry. Finally, mice were euthanized, and kidneys were preserved to assess renal inflammation.

Results:
At 4 months, a high salt diet did not modify blood pressure in any experimental group. However, male diabetic mice showed higher abundance of renal TNFα (1.8-fold increase,
P
<0.01), IL-6 (1.9 fold-increase,
P
<0.01) and IL-1β (2.1-fold increase,
P
<0.05) compared to equally treated diabetic females. Further, male diabetic mice displayed higher levels of renal NLRP3 inflammasome components such as pro-caspase-1 (3.9-fold increase) and NLRP3 (4.5-fold increase) compared to female diabetic mice (
P
<0.01). After an acute sodium challenge, diabetic male mice retained more sodium than diabetic females. Five hours after the saline injection, diabetic females eliminated 32 ± 3% of injected sodium while diabetic males eliminated only 23 ± 2% (
P
<0.01). Another set of mice at 7 months of age were exposed to a 4-week high salt diet. Now, diabetic males develop salt-sensitivity (MAP: 122 ± 2 mmHg) while females remained normotensive (MAP: 99 ± 3 mmHg) (
P
<0.01).

Conclusion:
Even in the absence of salt sensitivity, 4-month old diabetic males display renal inflammation and sodium retention. This is associated with the development of salt-sensitive hypertension at 7 months. Diabetic female mice are protected against the progression of diabetic nephropathy and do not develop salt sensitivity.
Abstract P3038: Reduced Renal Responsiveness and Altered Fluid Volume in an African Green Monkey (
Chlorocebus Aethiops Sabaeus)
Preeclampsia Model
Authors: Santillan Mark K , Scroggins Sabrina M , Weaver Chelsea C , Santillan Donna A , Taylor Jessica C , Osborn Jeffrey L
Published: September 2019

Preeclampsia is a prevalent, multi-organ complication of late pregnancy characterized by
de novo
gestational hypertension (GH) and proteinuria. Our group has demonstrated that arginine vasopressin (AVP) secretion, as measured by copeptin, is predictive of the development of human preeclampsia. Altered regulation of AVP early in gestation has been demonstrated in human preeclampsia. Recently, the nonhuman primate, African Green Monkey (AGM) has been characterized as a spontaneous, translational model of chronic hypertension, GH and preeclampsia. AGMs also have similar gestation and placentation to humans. We hypothesized that the AGM model of preeclampsia would demonstrate similar AVP related plasma and fluid volume changes as humans with preeclampsia. AGMs (n=10) were anesthetized with ketamine during late third trimester of pregnancy to obtain physiologic and obstetric measurements. Compared to normotensive (NT, n=4) third trimester pregnant females, GH females (n=6) had higher systolic and diastolic blood pressures (106 ± 5 vs. 162 ± 11 mmHg; 46 ± 4 vs. 86 ± 12, p=0.01) with no differences in heart rates (158 ± 4 vs. 169 ± 18 bpm, p=0.64). Consistent with other models of GH and preeclampsia, the GH AGM had decreased offspring birthweight in comparison to NT offspring (352 ± 11 vs. 275 ± 12 g, p=0.01). Further, plasma osmolality of GH females was higher in late third trimester compared to NT females (286 ± 11 vs. 312 ± 9 mOsm, p=0.05). This higher plasma osmolality was associated with the GH female’s trend to higher AVP secretion as measured by copeptin (2 ± 2 vs. 4 ± 1 ng/g, p=0.280). In contrast to human pregnancies, late third trimester plasma [Na
+
] of GH females was elevated compared to NT females (149 ± 3 vs. 157 ± 2 mMol/L, p=0.04). These data demonstrate that that the AGM model of preeclampsia replicates the plasma volume restricted findings consistent with human preeclampsia and possible insensitivity to control by AVP. Ongoing studies in early pregnancy will quantify changes in renal function during preeclampsia, differences in fluid volumes among NT and GH AGMs, and further the understanding of hormonal regulation of kidney function in the pathogenesis of preeclampsia in this translational AGM nonhuman primate.
Abstract P3040: High-Fat Feeding Reduces Cardiac Adaptation to Pregnancy in C57BL/6 Mice
Authors: Shoemaker Robin C
Published: September 2019

Objectives:
Maternal mortality during pregnancy is rising in the United States. Obesity is the most common problem in obstetrics associated with pregnancy complications. The adverse effects of obesity on cardiovascular health are well-known. However, there is a paucity of data describing the effects of obesity during pregnancy on cardiovascular function and structure. The purpose of this study was to test the hypothesis that obesity during pregnancy promotes impaired cardiac function in mice fed a high fat (HF) diet.

Methods/Results:
Female C57BL/6 mice (8 weeks old) were randomly assigned to receive a HF (60% kcal from fat; n=10) or control low fat (LF, 10% kcal from fat; n=10) diet. After 3 weeks of diet feeding, baseline echocardiography was performed on LF- and HF-fed female mice, after which females were crossed with male mice to become pregnant. Echocardiography was performed within 36 hours of birth. Left ventricular (LV) mass was increased with pregnancy in LF- and HF-fed mice (LF, baseline: 60.7 ± 1.6; LF, pregnancy: 73.0 ± 4.9; HF, baseline: 65.2 ± 3.1; HF, pregnancy: 78.4 ± 4.3 mg; P<0.01). In LF-fed mice, both stroke volume (SV) and ejection fraction (EF) were increased with pregnancy compared to baseline (SV, baseline: 21.8 ± 1.0; SV, pregnancy: 29.6 ± 1.5 uL; P<0.01; EF, baseline: 45.1 ± 2.5; EF, pregnancy: 56.1 ± 4.7 %; P<0.01). However, in HF-fed mice, neither SV nor EF were increased in response to pregnancy (SV, baseline: 24.1 ± 1.8; SV, pregnancy: 26.6 ± 1.5 uL; EF, baseline: 49.1 ± 0.7; EF, pregnancy: 47.6 ± 2.3 %).

Conclusions:
In response to pregnancy, cardiac function increased in lean mice. In contrast, cardiac function was not changed with pregnancy in HF-fed mice. These data suggest that HF-feeding during pregnancy may adversely impact maternal cardiovascular adaptation to pregnancy.
Abstract P3042: Novel Peptide B7-33 and It's Lipidated Derivative Protect Cytotrophoblasts From Preeclampsia Phenotype in a Cellular Model of the Syndrome
Authors: Afroze Syeda H , Pantho Ahmed F , Sprague David C , Kuehl Thomas J , Bathgate Ross , Zawieja David C , Hossain Mohammed A , Uddin Mohammad N
Published: September 2019

Background:
Preeclampsia (PreE) is a pregnancy disorder characterized by new onset of hypertension and reduced fetal weight. We have previously shown that marinobufagenin (MBG) and hyperglycemia impairs cytotrophoblasts (CTBs) function. The potential therapeutic role of H2 relaxin in PreE was reported, a novel H2 relaxin B-chain-only peptide B7-33 and its lipidated derivative have recently been developed. This study evaluates whether B7-33 and its lipidated derivative improve CTBs function and preE phenotype.

Methods:
A palmitic acid was attached at the N-terminus of B7-33. Human CTBs were treated with DMSO (vehicle) or 0.1, 1, 10 or 100 nM of MBG or with 100, 150, 200, 300, or 400 mg/dL glucose for 48h and were co-treated either with B7-33 (25 nM) or its lipidated derivative (25 nM) in the presence and absence of either MBG or hyperglycemia exposure. Some cells were pretreated with relaxin antagonist (1.0 μM RXFP1) prior to MBG or hyperglycemia exposure. Levels of vascular endothelial growth factor (VEGF), placental growth factor (PlGF), and soluble fms-like tyrosine kinase-1 (sFlt-1) were measured in culture media using ELISA kits. Statistical comparisons were performed using analysis of variance with Duncan’s post hoc test.

Results:
Lipidation of B7-33 results in a significant increase of half-life of B7-33 without altering its activity. Secretion of sFlt-1 was increased while VEGF and PIGF were decreased in CTBs treated with ≥1.0 nM MBG and ≥150 mg/dl of glucose (*p < 0.05 for each). Co-treatment with B7-33 (25 nM) and its lapidated derivative (25 nM) rescued CTBs from either MBG-induced and hyperglycemia-induced anti-angiogenic profile (p < 0.05 for each). B7-33 and its lapidated derivative cause an increase in the expression of VEGF in CTBs, however, they have no effect on other factors. The B7-33-induced upregulation of VEGF expression is attenuated by 1.0 μM RXFP1 antagonist.

Conclusion:
Both B7-33 and its lipidated derivative mitigate the MBG- and hyperglycemia-induced dysfunction of CTBs by attenuating anti-angiogenic phenotype similar to that seen in preE. Moreover, the B7-33 and its lipidated derivative induced effect on CTBs are attenuated by a relaxin antagonist. The preclinical study with B7-33 and its lipidated derivative are now underway.
Abstract P3046: Elevated Free Fatty Acids During Pregnancy Promote Vascular Impairment, Uteroplacental Dysfunction And Angiogenic Imbalance In Rats
Authors: Duncan Jeremy W , Bradshaw Jessica L , Spradley Frank T , Granger Joey P
Published: September 2019

Preeclampsia (PE) is a pregnancy-specific syndrome affecting 5-8% of pregnancies and is associated with vascular dysfunction and an increase in anti-angiogenic factors. Recent studies have shown that obese women are 4 times more likely to develop preeclampsia, and obesity/preeclampsia has been shown to increase circulating free fatty acids (FA). However, the role of FA on preeclamptic characteristics, such as uteroplacental and vascular dysfunction, as well as angiogenic imbalance has yet to be determined. To test the hypothesis that FAs induce a placental ischemic-like phenotype, pregnant rats were infused daily (IV) from gestational days (GD) 13-18 with specific free FA: 10mM Oleate and Palmitate, 4mM Linoleic Acid, and 0.8mM Arachadonic Acid. On GD 19, MAP, blood and tissues were collected. Third order mesentery arteries and aortas were used for vascular reactivity studies. Placental villi from normal pregnant rats exposed to FA
ex vivo
were examined for production of angiogenic factors. While infusion of FA resulted in no change in MAP, pup or placental weight, there was a trend for an increase in fetal reabsorption (9.7±3.3% vs 2.4±1.3%; p=0.07) and decrease in plasma PlGF in FA-infused rats (506±22vs 583±35 pg/mL; p=0.07), indicating moderate impairment in uteroplacental function in FA-infused pregnant rats compared to vehicle normal pregnant rats. Aortas of FA-infused pregnant rats revealed impaired Phe-induced vasoconstriction beginning at 3E
-6.5
M of Phe (31.3±7.5 vs 70.8±11.4; p=<0.02), while vasorelaxation was attenuated in mesenteric arteries of FA-infused pregnant rats compared to normal pregnant rats (p<0.01). Moreover, FA caused an increase in sFlt-1 (533±34 vs 181±7 pg/mL; p<0.01) and sFlt-1:PlGF ratio (4.8±.1 vs 3.2±.2; p<0.01) in placental explants compared to vehicle. These data suggest that elevated FA during pregnancy, at levels comparable to those observed in preeclampsia, promote uteroplacental dysfunction, angiogenic imbalance, and impaired vascular reactivity in rats. Further studies to examine the mechanisms associated with FA-induced uteroplacental outcomes in pregnancy could elucidate the role of elevated FA as a risk factor for placental ischemia.
Abstract P3049: A Novel Mobile App’s Reliability, End User Satisfaction, and Changes in Dash Diet Eating Patterns Over 8 Weeks
Authors: Steigerwalt Susan , Hummel Scott , DiFilippo Kristin , Scisney-Matlock Margaret
Published: September 2019

Objective:
To promote adherence to the Dietary Approaches to Stop Hypertension Diet (DASH) using a novel mobile app.

Methods:
The theory-grounded WHEELS for DASH app is designed to build enduring cognitive representations for long-term dietary behavioral changes. Users participated in twice-daily cognitive behavioral intervention activities,requiring a total of 8 minutes or less, over 56 days: these included goal setting, reading tailored DASH messages, and tracking eating patterns. Volunteers were recruited from an outpatient research registry, (N=72, age 19 to 73-mean=43, 78% female, 18% African American, 33% HTN diagnosis); 66 testers completed end of study surveys. A validated tool , App Quality Evaluation (AQEL), was used for intra-class correlation (ICC) reliability estimates and 95% confidence intervals based on a mean-rating (
k
=66), absolute-agreement, and 2-way random-effects model. One item, “How useful was the App in improving my daily healthy eating” measured end-user satisfaction. ANOVA analyses with Bonferroni correction were used to evaluate app-collected DASH eating behaviors over time.

Results:
Reliability estimates were excellent, (ICC[2,66]=.85; 95% CI .66 to .97,
p
<.001) and user satisfaction was good (75% ) rated very useful or useful. Key DASH eating patterns means significantly improved from week 1 to 6, and week 1 to 8, (Figure 1
,
p=< .001 and p=<.05. for all users who tracked daily DASH adherence).

Conclusion:
The WHEELS for DASH mobile application has potential to change dietary behaviors and support adherence to the DASH Eating Plan. The next step is to test this App for impact on blood pressure in patients with hypertension.
Abstract P3051: Are Black Hypertensive Patients Receiving Guideline-Recommended Medications?
Authors: Wozniak Gregory , Yang Jianing , Rakotz Michael
Published: September 2019

Objective:
Examine the prevalence of black hypertensive patients receiving guideline-recommended medication therapy for treating hypertension, either thiazide diuretics or calcium channel blocking agents (CCBs), alone or a component in single pill combination.

Study design:
Using 2011 and 2015 National Ambulatory Medical Care Survey data, we identified adult patient visits to non-federally employed office-based physicians, with a diagnosis of hypertension or when hypertension was the reason for the visit.

Population Studied:
2,454 adult hypertensive patient visits in 2011 (93.3 million weighted national estimates) and 2,648 in 2015 (141.9 million weighted national estimates).

Principal Findings:
Between 2011 and 2015, monotherapy prevalence was unchanged for non-Hispanic-blacks at 49%; non-Hispanic white monotherapy prevalence increased from 54% to 60%. However, in nearly 70% of visits, in both 2011 and 2015, blacks were prescribed an antihypertensive medication other than guideline recommended CCB or thiazide. The prevalence of CCB prescribing and thiazide diuretics precribing among blacks were both less than 20%. There is no difference between white patients and black patients in their shares of CCBs, thiazides and other monotherapy prescriptions in either year (Wald Chi-Square test
p
>.10).

Conclusions:
The majority of adult hypertensive patients are on monotherapy; black patients on monotherapy are not prescribed guideline recommended medication therapies, either CCB or thiazide diuretics. Hypertensive patients are getting similar pharmacological treatment across racial groups, though the guideline recommends are different for black patients.

Implications for Policy or Practice:
Black patients who are prescribed monotherapy as initial treatment and are not receiving guideline recommended medications nearly 69% of the time suggests that there are significant opportunities for improvement. Adoption of the 2017 ACC/AHA Guideline for High BP in Adults recommendation to lower the threshold for hypertension control from <140/<90 to <130/<80 mm is likely to have a greater impact on African Americans, compared to other populations and the focus on risk assessment will mean that more will receive treatment at a younger age.
Central Nervous System Electrical Stimulation for Neuroprotection in Acute Cerebral Ischemia
Authors: Bahr Hosseini Mersedeh , Hou Jesse , Bikson Marom , Iacoboni Marco , Gornbein Jeffrey , Saver Jeffrey L.
Published: September 2019

Background and Purpose—

Brain electrical stimulation, widely studied to facilitate recovery from stroke, has also been reported to confer direct neuroprotection in preclinical models of acute cerebral ischemia. Systematic review of controlled preclinical acute cerebral ischemia studies would aid in planning for initial human clinical trials.

Methods—

A systematic Medline search identified controlled, preclinical studies of central nervous system electrical stimulation in acute cerebral ischemia. Studies were categorized among 6 stimulation strategies. Three strategies applied different stimulation types to tissues within the ischemic zone (cathodal hemispheric stimulation [CHS], anodal hemispheric stimulation, and pulsed hemispheric stimulation), and 3 strategies applied deep brain stimulation to different neuronal targets remote from the ischemic zone (fastigial nucleus stimulation, subthalamic vasodilator area stimulation, and dorsal periaqueductal gray stimulation). Random-effects meta-analysis assessed electrical stimulation modification of final infarct volume. Study-level risk of bias and intervention-level readiness-for-translation were assessed using formal rating scales.

Results—

Systematic search identified 28 experiments in 21 studies, including a total of 350 animals, of electrical stimulation in preclinical acute cerebral ischemia. Overall, in animals undergoing electrical stimulation, final infarct volumes were reduced by 37% (95% CI, 34%–40%;
P
<0.001), compared with control. There was evidence of heterogeneity of efficacy among stimulation strategies (
I
2
=93.1%,
P
heterogeneity
<0.001). Among the within-ischemic zone stimulation strategies, only CHS significantly reduced the infarct volume (27 %; 95% CI, 22%–33%;
P
<0.001); among the remote-from ischemic zone approaches, all (fastigial nucleus stimulation, subthalamic vasodilator area stimulation, and dorsal periaqueductal gray stimulation) reduced infarct volumes by approximately half. On formal rating scales, CHS studies had the lowest risk of bias, and CHS had the highest overall quality of intervention-level evidence supporting readiness to proceed to clinical testing.

Conclusions—

Electrical stimulation reduces final infarct volume across preclinical studies. CHS shows the most robust evidence and is potentially appropriate for progression to early-stage human clinical trial testing as a promising neuroprotective intervention.
“Intellectual Silence” and Intellectual Endeavor in Medieval Slavia Orthodoxa
Authors: Romanchuk Robert
Published: September 2019

This survey of intellectual endeavor in medieval Slavia orthodoxa proposes a different way to think through the problem of the “intellectual silence of Old Rus′,” first set forth by Georges Florovsky and explored by George Fedotov, Francis Thomson, Simon Franklin, and now Donald Ostrowski. It examines the resources and opportunities for secondary schooling and their apparent outcomes in Kyivan Rus′ from the eleventh through the thirteenth century, among South Slavs on Mount Athos in the later fourteenth century, and at the Kirillo-Belozerskii (Kirillov) Monastery in northern Russia in the later fifteenth century. It concludes that intellectual endeavor is not necessarily bound to an international language of scholarship (e.g., Greek), one the one hand, or to a particular religious mentalité (e.g., that of the Western Church), on the other. Rather, it is cultivated by “schematizing” (educational) institutions oriented upon academic (heuristic) interpretive strategies and—most importantly—supported by textbooks and teachers.
First Record of the Ceratioid Anglerfish Species Gigantactis microdontis (Teleostei: Lophiiformes: Gigantactinidae) in the Western Pacific Ocean
Authors: PROKOFIEV ARTEM M. , PIETSCH THEODORE W.
Published: September 2019

The rare ceratioid anglerfish Gigantactis microdontis was formerly known from 12 specimens collected in the Eastern Pacific from 158° W eastward: off Hawaiian Islands, Oregon, California and Peru. Thirteenth specimen reported herein extends the known distribution of this species some 7630 km westward into the western tropical Pacific (off Caroline Islands). The newly reported specimen shows no principal differences in morphology from the previously known individuals.
Macropsini (Homoptera: Auchenorrhyncha: Cicadellidae: Eurymelinae) from the vicinity of Ambo, Ethiopia
Authors: TISHECHKIN DMITRI YU.
Published: September 2019

Macropsis tincta Tisheсhkin sp. n., M. viridofulgida Tisheсhkin sp. n., M. nikippa Tisheсhkin sp. n., and M. antibia Tisheсhkin sp. n. from the vicinity of Ambo, Ethiopia are described. Redescriptions of M. simplex Jacobi, 1910, M. tuberculata (Linnavuori, 1978), and M. hippodameia Linnavuori, 1978 based on the material from Ambo are given. Apparently, Indian and African Acacia-dwelling Macropsis species represent a separate lineage evolved on Mimosoidea, and dispersed throughout subtropical and tropical regions of the Old World. Acacia-dwelling group of Macropsis demonstrate some morphological trends unknown in Palaearctic species; this makes it necessary to re-evaluate the diagnostic significance of some morphological traits for the taxonomy of Macropsini.