bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 108: Prevalence and Characteristics of Cardiac Rehabilitation Participants With Resistant Hypertension
Authors: Laffin Luke J , Khan Asad , Lang Katherine , Van Iterson Erik H
Published: September 2019

Introduction:
The prevalence of apparent treatment resistant hypertension (RH) varies based on the population studied. We sought to determine the prevalence and characteristics associated with RH among patients enrolling in cardiac rehabilitation (CR).

Methods:
Between 2012 and 2017, 504 consecutive individuals at initial intake for entry into phase II CR were evaluated for RH. RH was defined as a participant taking 3 antihypertensive medications including a diuretic, with a resting systolic BP >130 mm Hg, or 4+ antihypertensive medications, regardless of BP. Participants with RH were compared to all other participants using student’s t-test or Fisher’s exact test as appropriate.

Results:
Sixty-three percent (320/504) of all CR participants carry a diagnosis of hypertension. Of those, 11% were classified as having RH (7% of all participants.) RH patients were more likely to be older, African-American, have higher SBP and higher pulse pressure. They also demonstrated an increased prevalence of co-morbid diagnoses, including heart failure with reduced ejection fraction, peripheral arterial disease, and type 2 diabetes mellitus (Table 1.) Only 3% of participants (1/36) with RH were prescribed a mineralocorticoid receptor antagonist, and only 14% (5/36) visited a hypertension specialist for consultation within a year of the initial CR appointment.

Conclusions:
The prevalence of RH amongst CR participants is 7%. RH participants have more co-morbidities than normotensive or non-resistant hypertensive counterparts. Given that CR participants are a high cardiovascular risk population, greater efforts to identify patients with RH, and refer for appropriate care are needed.
Abstract 128: Leptin Accelerates Autoimmune Disease Progression and the Development of Hypertension in an Experimental Model of Systemic Lupus Erythematosus
Authors: Taylor Erin , Ryan Michael
Published: September 2019

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that predominately affects women and is associated with high rates of hypertension and cardiovascular disease. SLE is characterized by B and T lymphocyte dysfunction and altered cytokine production, including elevated levels of the adipocytokine leptin. Leptin promotes the expansion of proinflammatory T

helper (T
H
) 1 and T
H
17 cells and inhibits the differentiation of regulatory T cells (T
REG
). Because T cells are mechanistically linked to the development of hypertension in SLE, we hypothesized that administration of leptin would alter T
H
subsets and accelerate the development of hypertension in a female mouse model of SLE. To test this hypothesis, 30 week old female SLE (NZBWF1, n=21) and control (NZW, n=25) mice were implanted with minipumps to continuously deliver recombinant mouse leptin (0.5 mg/kg/day) or vehicle for four weeks. At the conclusion of the study, splenic CD4
+
T
H
subsets were analyzed by flow cytometric analyses and no significant alterations in T
H
1, T
H
2, T
H
17, or T
REG
cells were detected; however, circulating T
REG
in SLE mice were lower after leptin administration (1.1±0.2% SLE-vehicle vs. 0.52±0.1% SLE-leptin, p<0.05). Circulating IgG isotypes were also analyzed to correlate with T
H
subset activities and circulating levels of IgG2a were higher in SLE mice administered leptin (0.79±0.2 mg/mL SLE-vehicle vs. 1.2±0.05 mg/mL SLE-leptin, p<0.05), indicating increased T
H
1 activity. In further support of inflammatory T cell activity, circulating levels of TNF-α and IL-17 were elevated in SLE mice administered leptin (TNF-α: 18.6±8.4 pg/mL SLE-vehicle vs. 80.5±15.9 pg/mL SLE-leptin, p<0.01) (IL-17: 0.46±0.1 pg/mL SLE-vehicle vs. 1.68±0.5 pg/mL, p<0.01). Mean arterial pressure (MAP; mmHg), measured in conscious mice by carotid catheter, was higher in SLE mice than in control mice (113±3 Control-vehicle vs. 128±3, p=0.06), and leptin further increased blood pressure in SLE mice (SLE-leptin: 134±3; p<0.01 vs. Control-vehicle and Control-leptin). In conclusion, these data suggest that leptin plays a pathogenic role in the development of hypertension in autoimmunity, in part by altering the balance of T
H
1, T
H
17, and T
REG
activity.
Abstract 136: The Ventromedial Hypothalamic BBSome is Required for Energy Homeostasis and Sympathetic Nerve Traffic Control
Authors: Guo Deng-Fu , Rouabhi Mohamed , Morgan Donald A , Rahmouni Kamal
Published: September 2019

The BBSome, a protein complex of 8 Bardet-Biedl Syndrome (BBS) protein including BBS1, has emerged as an important regulator of metabolic and cardiovascular function. We previously demonstrated that conditional disruption of the BBSome, by deleting the
Bbs1
gene, throughout the nervous system leads to obesity in mice. The ventromedial hypothalamus (VMH) play a key role in energy balance, but the contribution of the BBSome in the VMH to the control of energy homeostasis is not known. To address this, we specifically ablated the
Bbs1
gene in the VMH by crossing the Bbs1
fl/fl
mice with mice expressing Cre recombinase selectively in the VMH, driven by the steroidogenic factor 1 promoter (SF1
Cre
). VMH-selective Cre-recombination was verified using td-Tomato reporter mice. Importantly, SF1
Cre
/Bbs1
fl/fl
mice develop obesity as indicated by the increased (P<0.05) body weight (males: 43±2 vs 34±1 g in controls, and females: 33±2 vs 27±1 at age of 25 weeks) and fat mass (12.4±1 vs. 5.2±1 g). Of note, heterozygous SF1
Cre
/Bbs1
fl/wt
mice displayed an intermediate obesity phenotype (body weight: males: 39±2g and females: 30±1g). Daily food intake was not different in SF1
Cre
/Bbs1
fl/fl
mice relative to controls. However, energy expenditure (EE) was lower in SF1
Cre
/Bbs1
fl/fl
mice (ANCOVA corrected night EE: 0.27±0.06 vs 0.30±0.06 kcal/h in controls, P<0.05). Moreover, SF1
Cre
/Bbs1
fl/fl
mice exhibited a blunted cooling-induced increase in sympathetic nerve activity (SNA) subserving thermogenic brown adipose tissue (BAT), although basal BAT SNA activity was not different. Next, we assessed the consequence of SF1 neuron-specific
Bbs1
gene deletion on SNA subserving cardiovascular beds. SF1
Cre
/Bbs1
fl/fl
mice displayed a modest, but significant increase in renal SNA (49±24%, P=0.03) and splanchnic SNA (85±18%, P<0.05), but not lumbar SNA (11±9%, P=0.14). Blood pressure, recoded under anesthesia, was not different in SF1
Cre
/Bbs1
fl/fl
mice relative to controls (P=0.2). Radiotelemetry measurement of blood pressure in SF1
Cre
/Bbs1
fl/fl
and control mice is under way. These findings highlight the importance of the VMH BBSome for the regulation of energy homeostasis and sympathetic nerve outflow.
Abstract 137: Impact of Leptin Deficiency Compared to Neuronal Specific Leptin Receptor Deletion on Cardiometabolic Regulation
Authors: do Carmo Jussara M , da Silva Alexandre A , Gava Fabio N , Moak Sydney P , Dai Xuemei , Hall John E
Published: September 2019

The main goal of this study was to compare the impact of whole-body leptin deficiency with neuronal specific leptin receptor (LR) deletion on metabolic and cardiovascular regulation. Liver fat, diacylglycerol acyltransferase-2 (DGTA2) and CD36 protein content were measured in male and female wild-type (WT, n=5/sex), nervous system LR deficient (LR/Nestin-Cre, n=6/sex), and leptin deficient (ob/ob, n=5) mice. Blood pressure (BP) and heart rate (HR) were recorded by telemetry, and motor activity (MA) and oxygen consumption (VO
2
) were monitored at 24 weeks of age. Female and male LR/Nestin-Cre and ob/ob mice were heavier than WT mice (62±5 and 61±3 vs 31±1 g), hyperphagic (6.2±0.5 and 6.1±0.7 vs 3.5±1.0 g/day), with reduced VO
2
(27±1 and 33±1 vs 49±3 ml/kg/min) and decreased MA (3±1 and 7±2 vs 676±105 cm/hr). LR/Nestin-Cre and ob/ob mice were also hyperinsulinemic and hyperglycemic compared to WT mice. LR/Nestin-Cre mice had high plasma leptin levels while ob/ob mice had undetectable leptin levels. Despite comparable obesity, LR/Nestin-Cre mice had lower liver fat content (83% reduced) and DGTA2 and CD36 protein levels than ob/ob mice. Male WT, LR/Nestin-Cre, and ob/ob mice exhibited similar BP (111±3, 110±1 and109±2 mmHg), whereas female LR/Nestin-Cre mice had higher BP compared to WT females despite similar metabolic phenotypes compared to male LR/Nestin-Cre mice. No significant increases in plasma aldosterone concentration was observed in male LR/Nestin-Cre compared to WT mice (495±48 vs. 440±62 pg/ml); however, female LR/Nestin-Cre mice had ~14 fold higher plasma aldosterone concentration compared to female WT mice (707±97 vs. 50±3 pg/ml). These results indicate that although nervous system LRs play a crucial role in regulating body weight and glucose homeostasis, peripheral LRs also regulate liver fat deposition and modulate BP in a sex dependent manner. (NHLBI-PO1HL51971, NIGMS P20GM104357 and U54GM115428)
Abstract 144: Macula Densa NOS1β-Mediated TGF Response Plays an Important Role in the Sex Differences in Salt-Sensitive Hypertension
Authors: Zhang Jie , Wei Jin , Jiang Shan , Wang Lei , Liu Ruisheng
Published: September 2019

Females are resistant to salt-sensitive hypertension than males, but the mechanisms are not completely elucidated. We recently demonstrated that a decisive role of macula densa neuronal nitric oxide synthase β (NOS1β) in the tubuloglomerular feedback (TGF) response, long-term control of glomerular filtration rate (GFR), sodium excretion and blood pressure. Thus, in this study, we tested a hypothesis that high salt diet-induced upregulation of NOS1β in the macula densa is exaggerated in females than males, which induces more inhibition in TGF response, thereby facilitating sodium excretion and contributing to the resistance to salt-sensitive hypertension. We used microperfusion, micropuncture, clearance of FITC–insulin and radio telemetry to examine the sex differences in macula densa NOS1β expression, nitric oxide (NO) generation, TGF response, kidney clearance function and mean arterial pressure (MAP) in response to a high salt diet in C57BL/6 and macula densa–specific NOS1 knockout (KO) mice. In C57BL/6 mice, males and females had comparable basal levels in macula densa NOS1β expression, NO generation, TGF response and MAP. An 2-week high salt diet resulted in more increases of NOS1β expression in female mice than male mice (3.4±0.3-fold vs. 1.7±0.1-fold), greater increases of NO generation by the macula densa in female mice than male mice (99.1±19.8 % vs. 55.6±11.6 %), and more attenuation in TGF responses
in vivo
(48.7±7.2 % vs. 25.5±2.9 %) as well as TGF response
in vitro
(58.5±5.6 % vs. 33.7±9.3 % )in female mice than male mice. Additionally, in response to a 2-week high salt diet along with low dose Ang II, the MAP increased by 13.7±4.2 mmHg in females and 35.4±5.6 mmHg in males with a sex difference of 21.7±4.7 mmHg. In the KO mice, the high salt diet had no significant effects on the macula densa NOS1β expression, NO generation, TGF response
in vivo
or
in vitro
in both females and males. Moreover, in response to the high salt diet along with low dose Ang II, the MAP increased by 41.7±4.1 mmHg in KO females and 52.6±3.8 mmHg in KO males with a sex difference of 10.9±3.1 mmHg, which was significantly reduced compared with C57BL/6 mice. In conclusion, macula densa NOS1β-mediated TGF response plays an important role in the sex difference in salt-sensitive hypertension.
Abstract 145: Knockout of Gamma-
Adducin
Impairs Vascular Function in Renal Arterioles in Association With Htn-Induced Renal Injury
Authors: Gao Wenjun , Fan Letao , Zhang Huawei , He Xiaochen , Wang Shaoxun , Ya Guo , Roman Richard J , Fan Fan
Published: September 2019

The FHH rat is a genetic model of hypertension that develops proteinuria, glomerulosclerosis, and chronic kidney disease. However, the genetic causes are unknown. We have previously identified an inactivating mutation of
Add3
in FHH rats in association with reduced
ADD3
expression and impaired myogenic reactivity of the renal arterioles. The vascular impairment and renal dysfunction were restored with knock-in of wild type (WT)
Add3
in FHH rats. The present study examined whether knockout (KO) of
Add3
in normal WT rats impairs the myogenic response of renal afferent arteriole (Af-art), interlobular arteriole (IA), arcuate arteriole (AA), renal blood flow (RBF) autoregulation, and if the reduction of expression of ADD3 promotes hypertension-induced renal dysfunction. Blood pressure was similar in 24-week old
Add3
KO vs. WT rats, and after induction of 3 weeks of DOCA-salt-hypertension in these strains. Proteinuria was significantly higher in both normotensive and hypertensive
Add3
KO compared with WT rats. KO of
Add3
abolished the myogenic response of Af-art compared with WT rats. Similarly, the diameters of IA and AA increased 46 % (from 55.28 ± 2.95 um to 80.39 ± 0.41 um) and 25 % (from 92.57 ± 9.51 um to 115.49 ± 11.68 um) respectively in
Add3
KO rats (n=4), while they remained unchanged in WT (n=5). Moreover, KO of
Add3
abolished the RBF autoregulation compared with WT rats. These results indicate that KO of
Add3
plays an important role to reduce the myogenic reactivity of renal arterioles and RBF autoregulation, and enhances renal damage after the onset of hypertension.
Abstract 148: Sex-Differences in Fetal Programming of Cardiomyopathy Induced by Hypertensive Disorders of Pregnancy in Mice
Authors: Benizri Nissim , Raguema Nozha , Marc Casandra , Pépin Émilie , Lavoie Julie , Bertagnolli Mariane
Published: September 2019

Background:
Hypertensive disorders reach one in ten pregnancies worldwide, significantly increasing rates of maternal and neonatal morbidity and mortality. Children born to hypertensive pregnancies can develop special clinical features that are consistent with a preterm or accelerated aging process with signs of cardiac remodeling as early as childhood. The aim of this study was to develop a new ultrasound imaging protocol to describe sex-differences in the fetal programming of cardiomyopathy in a genetic mice model of maternal hypertension and superposed pre-eclampsia.

Methods and Results:
We have performed fetal echocardiography imaging in n=4/group transgenic mice overexpressing human renin+angiotensinogen versus controls (C57BL/6) at 18.5 gestational days. Fetal images were adjusted by intracranial diameter as an intrauterine marker of fetal growth. Male and female offspring (n=8/group/sex) were followed by echocardiography up to 40 postnatal days. Data are average±SD. Fetuses of hypertensive mothers had thicker left ventricular (LV) walls (0.32±0.02 vs 0.45±0.04mm, P<.01) and more dilated chamber (0.82±0.02 vs 0.97±0.07mm, P<.01), with larger LV mass (3.2±0.4 vs 4.3±0.3mg, P<.001) compared to controls, which remained significant after adjusting for intracranial diameters. Into adulthood, male and female offspring of hypertensive mothers had greater LV mass (male: 88±19 vs 139±62mg, P<.01; female: 74±21 vs 104±27, P<.05) and wall thickness (male: 0.70±0.03 vs 0.95±0.22mm, P<.05; female: 0.63±0.15 vs 0.91±0.17mm, P<.05) compared to control offspring. However, females had additional LV chamber dilation (3.3±0.3 vs 3.9±0.4mm, P<.05) and reduced fraction of shortening (48±9 vs 33±4%, P<.01) compared to controls, indicating LV systolic dysfunction and cardiomyopathy only in in this offspring group but not in males.

Conclusion:
Our results demonstrate the feasibility of using fetal and postnatal echocardiography to evaluate the programming of cardiomyopathy in mice exposed to hypertensive pregnancy. In addition, we showed that fetal cardiac remodeling changes persisted into adulthood in offspring of hypertensive mothers, which in females has further progressed to an accelerated cardiomyopathy programming.
Abstract 149: Postpartum Cognitive Function in Young Women With a History of Preeclampsia: Association With Blood Pressure but Not Large Artery Stiffness
Authors: Nuckols Virginia R , Stroud Amy K , Brandt Debra S , DuBose Lyndsey E , Santillan Mark K , Santillan Donna A , Pierce Gary L
Published: September 2019

Introduction:
Women with a history of preeclampsia (PE) have elevated large artery stiffness and blood pressure (BP) several years postpartum. Age-related increases in aortic stiffness are deleterious to brain structure and cognitive function; however, the relationship between large artery stiffness and cognitive function has not been assessed in women with a history of PE. The purpose of this study was to determine the extent to which large artery stiffness and BP are associated with cognitive function in women with a history of PE.

Methods:
Women with a history of PE (n=12; age 33±1 yrs; BMI 28.5±3.1 kg/m
2
) and healthy pregnancy controls (n=7; age 34±2 yrs; BMI 26.5±4.0 kg/m
2
) were assessed one year postpartum. Brachial BP was collected in triplicate using an automated cuff. Aortic stiffness was measured via applanation tonometry and quantified as carotid-femoral pulse wave velocity (cfPWV). Carotid stiffness (β-stiffness) was obtained via ultrasonography and carotid tonometry. Cognitive function was assessed in domains of memory, processing speed, and executive function.

Results:
Women with a history of PE had higher systolic BP (121±4 vs. 104±3 mmHg, p<0.01) and cfPWV (6.2±0.4 vs. 5.1±0.2 m/s, p=0.06), though the latter did not reach statistical significance. There was no difference between groups in β-stiffness (6.1±0.4 vs. 6.1±0.6 U, p=0.97). Cognitive domains of executive function, memory, and processing speed did not differ between groups (all p>0.05). Systolic BP was associated with reductions in executive function (r = -0.52, p=0.04) independent of education level, but was not related to reductions in memory or processing speed. Arterial stiffness was not associated with cognition.

Conclusions:
Women with a history of PE had elevated systolic BP and aortic stiffness, but only BP was associated with reductions in executive function. These preliminary findings suggest that young women with a history of PE may be vulnerable to reductions in cognitive function related to persistent elevated systolic BP.
Abstract P101: Interleukin 17 Signaling Mediates Cytolytic Natural Killer Cell Activation in Response to Placental Ischemia
Authors: Cornelius Denise C , Travis Olivia K , White Dakota , Baik Cedar H , Thompson Willie L , Giachelli Chelsea , Williams Jan M , LaMarca Babbette
Published: September 2019

The
R
educed
U
terine
P
erfusion
P
ressure (RUPP) rat model of placental ischemia mimics many characteristics of preeclampsia (PE) including hypertension, fetal growth restriction, and increased T
H
17s, IL-17, and cytolytic natural killer cells (cNKs). IL-17 stimulates NK cytotoxicity
in vitro
. This study tested the hypothesis that blockade of IL-17 signaling would inhibit activation of cNKs to improve blood pressure and fetal growth in RUPP rats. On gestation day (GD) 14, osmotic pumps infusing IL-17 RC (100 pg/d), a soluble receptor for IL-17, were implanted into pregnant rats undergoing RUPP (RUPP+IL17 RC). On GD 19, circulating and placental T
H
17s and cNKs were quantified via flow cytometry in normal pregnant (NP), RUPP, and RUPP+IL17 RC rats. cNK activation, placental ROS, fetal and placental weights, and MAP were also assessed. As we have previously shown, placental T
H
17 populations (% gated) were significantly increased in RUPP (23.1±3.9%, n=9) compared to NP (8.5±3.9%, n=9) rats and were suppressed in RUPP+IL17 RC (8.3±3.1%, n=9). Circulating T
H
17s followed the same trend. Placental cNKs, significantly increased from 7.2±2.8% in NP to 16.6±3.3% in RUPP, and were normalized to 7.2±2.8% after IL-17 blockade (p<0.05 vs RUPP). Placental cNK proteins and circulating cNKs showed a similar trend. Placental levels of the cNK cytokine, TNFα, increased from 28.5±.01 pg/mg in NP to 46.2±6.0 pg/mg in RUPP and was normalized to 28.5±4.6 pg/mg in RUPP+IL-17 RC (p<0.05 vs RUPP). Placental MIP3a, a cNK chemokine, had a similar trend. Assessment of
in vitro
cytotoxic activity of placental NK cells from rats in each group demonstrated a 5-fold increase in cytotoxicity by RUPP NK cells compared to NP NK cells. This was blunted in NK cells from RUPP+IL17 RC rats. Placental ROS was increased in RUPP compared to NP and significantly decreased with IL-17 blockade. Fetal weight decreased from 2.4±0.04 g in NP to 2.1±0.04 g in RUPP and increased to 2.3±0.05 g in RUPP+IL17 RC (p<0.05 vs RUPP). Placental weights followed a similar trend. MAP increased from 93 mmHg in NP to 120 mmHg in RUPP, and was decreased to 105 mmHg in RUPP+IL17 RC (p<0.05 vs RUPP). These data demonstrate a direct role for IL-17 signaling to mediate NK cytotoxic activation in response to placental ischemia during pregnancy.
Abstract P107: Role for Endothelin B Receptors in the Maintenance of Heart Rate Baroreflex Function
Authors: Becker Bryan K , Jin Chunhua , Pollock David M
Published: September 2019

Rats lacking functional endothelin B (ET
B
) receptors are hypertensive, salt-sensitive, and have increased sympathetic tone. Hypertension is also associated with blunted arterial baroreflex sensitivity that can lead to increased cardiovascular risk. Although the endothelin system has been implicated to play a role in baroreflex sensitivity, the role of ET
B
receptors has not been clearly elucidated. We hypothesized that ET
B
receptors are necessary for appropriate baroreflex sensitivity. We tested this hypothesis using selective pharmacological blockade of the ET
B
receptor and using rats that lack functional ET
B
receptors except in adrenergic tissues (ET
B
-def rats on WKY background). Anesthetized Sprague-Dawley rats given an intravenous infusion of the ET
B
receptor antagonist, A-192168 (10 mg/kg), had a blunted heart rate response to phenylephrine-induced pressor ramp compared to post-vehicle baseline (-0.08 ± 0.03 vs. -0.22 ± 0.04 bpm/mmHg; p = 0.048, n = 4). Similarly, anesthetized ET
B
-def rats had a blunted heart rate response to phenylephrine compared to transgenic controls (0.21 ± 0.07 vs. -0.18 ± 0.04 bpm/mmHg; p = 0.001, n = 3-6/group). ET
B
-def and transgenic control rats were instrumented with telemetry transmitters (HD-S10 Data Sciences), and mean arterial pressure was recorded for 24 hours and analyzed in 10 second bins. ET
B
-def rats (n = 6) displayed a significantly higher blood pressure lability compared to transgenic controls (n = 5) as shown by a higher standard deviation of mean arterial blood pressure (11.6 ± 0.2 vs 9.7 ± 0.2 mmHg; p < 0.001) and a greater range of mean arterial blood pressure (85.3 ± 4.0 vs. 68.4 ± 3.6 mmHg; p = 0.01). This increased lability of blood pressure in conscious ET
B
-def rats is consistent with baroreflex dysfunction. These data support the hypothesis that ET
B
receptors are integral for appropriate heart rate baroreflex function.
Abstract P109: Hypertension in a Large Cohort of Patients With Lipoprotein(a) at a Tertiary Academic Center
Authors: Sheth Samip , Risman Marjorie , Rader Daniel , Jacoby Douglas
Published: September 2019

Background:
Recently, guidelines have recognized elevated Lp(a) as a clinical risk factor significantly and independently associated with cardiovascular disease (CVD). Another important CVD risk factor, hypertension, has been well-described. However, few real-world studies that explore the association between lipoprotein(a) and hypertension have been conducted.

Objective:
To evaluate hypertension in patients with serum lipoprotein(a) [Lp(a)] at a large tertiary academic center.

Methods:
The University of Pennsylvania Health System was queried for all patients with an Lp(a) result between 1999-2019. The first Lp(a) result was chosen for patients with multiple Lp(a) results. In this cohort of patients, the presence of hypertension was queried by hypertension ICD-9 and ICD-10 codes. The cohort was stratified by Lp(a) tertile and the presence of hypertension was evaluated. A chi-squared analysis was performed to test for association between Lp(a) tertile and presence of hypertension.

Results:
The query returned a cohort of 8120 patients with a median and interquartile range of Lp(a) of 22 mg/dL and 8-64 mg/dL, respectively. The cohort had a median age of 54 years, 54% (n=4379) were men, and 21% (n=1705) were non-white. Hypertension was reported in 51% (n=4155) of patients. The tertile with low Lp(a) [median, 6 mg/dL; IQR, 4-8 mg/dL] had hypertension in 50.1% (n=1357) of patients. The tertile with moderate Lp(a) [22 mg/dL, 16-33 mg/dL] had hypertension in 50.5% (n=1367) of patients. The tertile with high Lp(a) [84 mg/dL, 64-116 mg/dL] had hypertension in 51.0% (n=1381) of patients. The association between Lp(a) tertile and presence of hypertension was insignificant (
p-value,
0.81).

Conclusions:
In this real-world cohort, the data suggest that Lp(a) and hypertension are not associated. New clinical trials that test Lp(a)-lowering pharmacotherapies may enable further characterization of the association between Lp(a) and hypertension in order to inform CVD prevention.
Abstract P1101: Hormonal Contraceptive Use, Arterial Stiffness and Renin Angiotensin System Activity in Women
Authors: Kalenga Cindy , Dumanski Sandi , Ramesh Sharanya , MacRae Jennifer M , Nerenberg Kara , Metcalfe Amy , Sola Darlene , Ahmed Sofia B
Published: September 2019

Background:
Oral contraceptive use is associated with increased CV risk. Whether non-oral hormonal contraceptive use poses a similar risk is unclear.

Objectives:
To evaluate the association between oral and non-oral hormonal and arterial stiffness and renin-angiotensin system (RAS) activity in premenopausal women.

Methods:
Healthy premenopausal women using non-oral hormonal contraception (NOHC), oral hormonal contraception (OC) (minimum duration of 3 months) and controls were studied in a fasting, high-salt state. Aortic augmentation index (AIx) and pulse wave velocity (PWV) were measured at baseline and in response to Angiotensin II (AngII) challenge, a validated marker of arterial RAS activity. Results from the 3 groups were compared using ANOVA and presented as mean and standard error.

Results:
Fifty-six women (6 OC, 8 NOHC, 42 controls) were studied. Women were similar in age (OC 29±7yvs NOHC 28±4yvs controls 32±2y, p=0.52)and BMI (OC 26.7±1vsNOHC 22.3±2vs controls25.3±4, p=0.12). No differences were observed amongst the groups with regards to baseline arterial stiffness measures (AIx: OC 4.08±1%; NOHC -2.75±2%; controls 9.01±3%; p =0.10; PWV: OC 6.94±3 m/s; NOHC 6.4±2 m/s; controls 8.04±5m/s; p=0.49). In response to AngII challenge, NOHC users had a greater change in AIx compared to OC after adjustment for age and blood pressure (NOHC 17.06±3%; controls 9.76±1%; p=0.048). No significant changes in PWV were observed among NOHC or OC and controls.

Conclusions:
Arterial RAS is lower in non-oral hormonal contraceptive users, suggesting this may be a safer contraception option in women at high risk of CVD.
Abstract P1104: The Infusion of the Soluble Prorenin Receptor Increases Blood Pressure in High-Fat Fed Male Mice
Authors: Gatineau Eva O , Gong Ming , Yiannikouris Frederique B
Published: September 2019

Obesity-related hypertension is a major public health concern. We recently demonstrated that plasma levels of the soluble form of the prorenin receptor (sPRR) were elevated in obesity. In the present study, we aimed to determine whether sPRR contributed to blood pressure (BP) elevation in the context of obesity. High-fat fed C57BL/6 male mice were infused with vehicle (Veh) or sPRR (sPRR, 30 μg/kg) via subcutaneously implanted osmotic minipump for 4 weeks. BP parameters were recorded using radiotelemetry devices (n=6/groups). Male mice infused with sPRR exhibited higher systolic blood pressure (SBP. Veh: 133±1 mmHg, sPRR: 141±2 mmHg, P<0.05) and mean arterial pressure (MAP. Veh: 116±1 mmHg, sPRR: 124±2 mmHg, P<0.05) and lower spontaneous baroreflex sensitivity (Veh: 3.8±1.2 ms/ mmHg, sPRR: 2.1±0.5 ms/ mmHg, P<0.05) than mice infused with vehicle. To define mechanisms involved in BP elevation, mice were injected with an angiotensin-II type 1 receptor antagonist (losartan), a muscarinic receptor antagonist (atropine), a β-adrenergic antagonist (propranolol) and a ganglionic blocker (chlorisondamine). Losartan did not blunt sPRR-induced elevation in SBP. However, SBP response to angiotensin II was increased in mice infused with sPRR suggesting that AngII could potentiate sPRR-induced elevation in SBP. Chlorisondamine treatment exacerbated the decrease in mean arterial pressure in male mice infused with sPRR compared with vehicle (MAP. Veh: -21±1 mmHg, sPRR: -29±1 mmHg, P<0.05). Overall, we demonstrated that sPRR increased SBP through an impairment of the baroreflex sensitivity and an increase in the sympathetic tone in high-fat fed C57BL/6 male mice.
Abstract P1107: Acute Psychosocial Stress Increases Circulating Inflammatory Mediators in the Humanized Sickle Cell Mouse Model
Authors: Molina Patrick , Fox Brandon , Sedaka Randee , Becker Bryan , Kasztan Malgorzata , Botta Davide , Allan J. Miller , Pollock David , Pollock Jennifer
Published: September 2019

Vaso-occlusive crisis often occurs in sickle cell disease (SCD). Since psychosocial stress leads to impaired vascular function and inflammation, we hypothesized that acute psychosocial stress elicits an exaggerated blood pressure response and/or increased circulating inflammatory mediators in a mouse model of SCD. We utilized adult male (16-20 wks) humanized Townes sickle cell (HbSS) and control (HbAA) mice with telemetry (n=8) to monitor changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), spectral analysis (low frequency/high frequency, LF/HF ratio) of blood pressure variability, heart rate (HR), and locomotor activity (LA) in response to cage switch stress (CSS). CSS-induced increases in DBP were significantly attenuated in HbSS versus HbAA (HbSS: 23.3±1.8mmHg, HbAA: 31.6±1.7mmHg, p=0.004), while the increase in SBP was similar in HbSS and HbAA. CSS increased LF/HF in both strains, although HbSS was significantly less than HbAA (CSS
HbAA
: 3.21±0.2; CSS
HbSS
: 1.68±0.2, p<0.05). Increases in HR and LA were similar in HbSS and HbAA. Separate groups (n=6-7) were used to assess circulating inflammatory mediators (39-plex Luminex, ng/mL) at baseline (BL) and 30-min post-CSS. Interestingly, eotaxin (HbAA: 1.4±0.1, HbSS: 0.6±0.07, p<0.0001), plasminogen activator inhibitor-1 (PAI-1) (HbAA: 0.07±0.004, HbSS: 0.5±0.1, p=0.001), P-selectin (HbAA: 29±2.7, HbSS: 36±1.5, p=0.05), and soluble intercellular adhesion molecule-1 (sICAM-1) (HbAA: 2.4±0.05, HbSS: 2.9±0.2, p=0.04) were significantly higher in HbSS at BL. CSS significantly reduced eotaxin in HbAA mice (BL: 1.4±0.1, CSS: 1.1±0.08, p=0.02), whereas there was no change in HbSS mice. IL-6, CXCL1, sICAM-1, and PAI-1 were not changed in HbAA mice following CSS, but were significantly elevated following CSS in HbSS mice (IL-6: BL: 0.037±0.008, CSS: 0.065±0.005, p=0.01; CXCL1: BL: 0.11±0.02, CSS: 0.25±0.05, p=0.01; sICAM-1: BL: 2.9±0.2, CSS: 3.7±0.3, p=0.05; PAI-1: BL: 0.54±0.12, CSS: 1.17±0.24, p=0.007). The reduced response in DBP to CSS in HbSS mice is consistent with impaired vascular function. Further, exaggerated changes in select inflammatory mediators in response to CSS provide a potential link for psychosocial stress to vaso-occlusion and organ damage in SCD.
Abstract P1113: P2x7 Receptor Plays a Role in Angiotensin II-Induced Hypertension and Vascular Remodeling
Authors: Shokoples Brandon , Paradis Pierre , Schiffrin Ernesto L
Published: September 2019

Introduction:
Inflammasome activation by binding of ATP released from damaged cells to the purinergic receptor P2X7 (P2RX7) could play a role in hypertension and vascular injury through release of interleukin (IL)-1β and immune cell activation. Elevated ATP levels were observed in the renal interstitial fluid of angiotensin (Ang) II-infused rats, and treatment of these rats with a non-selective P2 receptor blocker prevented Ang II-induced inflammation and renal damage. P2RX7 knockout (

P2rx7
–/–

) prevented deoxycorticosterone acetate-salt-induced blood pressure (BP) elevation and renal damage. However, it is unknown whether P2RX7 plays a role in Ang II-induced BP elevation and vascular damage. We hypothesize that Ang II-induced hypertension, vascular injury, and inflammation will be blunted in

P2rx7
-/-

mice.

Methods:
Ten to 12-week-old male C57BL/6J male wild-type (WT) and

P2rx7
–/–

mice were sham-treated or infused with Ang II (490ng/kg/min) for 14 days. BP was determined by telemetry. Mesenteric artery function and remodeling was assessed using pressurized myography. P2RX7 expression in spleen immune cells was determined by flow cytometry. IL-1β secretion from bone marrow-derived macrophages (BMDM) isolated from WT and

P2rx7
–/–

mice was assessed by ELISA.

Results:
Stimulation with lipopolysaccharides and ATP caused IL-1β release in WT (339±162 pg/mL) but not

P2rx7
–/–

BMDMs. In WT mice, Ang II increased P2RX7 expression in dendritic cells (mean fluorescence intensity: 1927±120 vs 3983±983) and macrophages (2541±265 vs 3314±273 respectively).
P2rx7
knockout reduced Ang II-induced systolic (159±3 vs 165±7 mm Hg) and diastolic BP elevation (110±4 vs 126 ±7 mm Hg) compared to WT mice. Acetylcholine-induced vascular relaxation was unaffected by Ang II or
P2rx7
knockout. Ang II increased the media-to-lumen ratio in WT (4.71±0.18% vs 3.89±0.21%,
P
<0.01) but not in

P2rx7
–/–

mice.

Conclusion:
This study demonstrated that P2RX7 plays a role in Ang II-induced hypertension and vascular remodeling.
Abstract P113: Anti-Hypertensive Properties of Brown Adipose Tissue
Authors: Zhang Jie , Oydanich Marko , Nishimura Koichi , Berkman Tolga , Vatner Dorothy E , Vatner Stephen F
Published: September 2019

The regulator of G protein signaling 14 (RGS14) knockout (KO) mice live longer than their wild type (WT) littermates and are protected against myocardial infarction, diabetes and obesity, and reduced exercise tolerance; all features of cardiovascular risk protection and healthful aging. The major mechanism mediating these features of healthful aging is their brown adipose tissue (BAT), since after BAT removal, the RGS14 KO mice lose these features of healthful aging. The goal of this investigation was to determine if the RGS14 KO and its BAT is a unique mechanism to protect against hypertension. Angiotensin II was chronically infused by osmotic pumps (1.44 mg/kg/day) for 2 wks. Mean arterial pressure (MAP) was measured by tail-cuff, stroke volume was measured by cardiac echocardiography. Cardiac output was calculated as the product of stroke volume and heart rate and total peripheral resistance (TPR) was calculated as mean MAP/cardiac output. There were no differences in baseline heart rate (434 ± 19 vs 439 ± 18 beats/min), MAP (82 ± 3.0 vs. 87 ± 1.8 mmHg), and TPR (3.8 ± 0.3 vs 3.9 ± 0.3 mmHg/mL/min) in RGS14 KO and WT prior to the angiotensin II. After 2 weeks of angiotensin II MAP and TPR rose by 70 ± 10.4 % and 43 ± 11.2%, respectively in WT. Surprisingly, in RGS14 KO 2 weeks of angiotensin II increased MAP significantly less, p<0.05, than WT, i.e., by only 11 ± 6.5%, and TPR did not increase at all. Transplantation of BAT to WT recipients also significantly diminished, p<0.05, the hypertensive effects of angiotensin II, with BAT donors exhibiting increased MAP by 70% and TPR by 78%, but in BAT recipients MAP rose by only 23% and TPR rose by only 6.5%. The second goal was to determine if BAT protects against hypertension through angiogenesis/arteriogenesis, a potential mechanism mediating protection against hypertension. Both VEGF and eNOS increased, p<0.05, in RGS14 KO BAT tissues. Thus, inhibition of RGS14 and BAT are novel mechanisms to protect against hypertension.
Abstract P116: Inhibition of Ang II-Induced Mitochondrial Fission and Endoplasmic Reticulum Stress Attenuates Protein Aggregate Accumulation, Inflammation, and Senescence in Vascular Smooth Muscle Cells
Authors: Cicalese Stephanie M , Cooper Hannah , Kawai Tatsuo , Miyao Masashi , Preston Kyle , Rizzo Victor , Scalia Rosario , Eguchi Satoru
Published: September 2019

Aging is a non-modifiable risk factor for most cardiovascular diseases (CVDs) including hypertension and abdominal aortic aneurysms (AAA). As much as 14-year difference was noted in vascular aging assessed by arterial stiffness in healthy middle age human population, suggesting that premature vascular aging is a promising therapeutic target to combat against CVD. The molecular mechanisms involved in Ang II induction of premature vascular aging and how these contribute to CVD development are poorly understood. The objective of this study was to elucidate involvement of mitochondria and endoplasmic reticulum (ER) dynamics in Ang II-induced senescence in vascular smooth muscle cells (VSMCs), and how these contribute to CVDs. Ang II is known to promote mitochondrial fission and increases oxidative stress, and subsequent ER stress. Thus, chronic activation of Ang II signaling has been reported here to cause proteotoxicity due to accumulation of protein aggregates. Sodium 4-phenylbutyrate (PBA) increases ER folding capacity to restore proper protein folding and attenuate activation of UPR. Our
in vitro
data show Ang II enhances protein aggregate formation and PBA pretreatment alleviates their cellular accumulation in both size and number. Treatment of rat aortic VSMCs with 4-PBA or mitochondrial fission inhibitor mdivi1 mitigates Ang II induced VSMC senescence, detected by 4% (p=0.04) and 5% (p=0.02) reduction in senescence-associated β galactosidase (SA-β gal) positive cells, respectively. Ang II induced VSMC inflammation was monitored by THP-1 adhesion assay with a 1.87 fold increase in leukocyte adhesion (p=0.017), which was attenuated by PBA.
In vivo
, male C57/B6 mice infused with Ang II (4 weeks) with beta-aminopropionitrile (drinking water) (AAA model) +/- mdivi1 25 mg/kg IP 3x per week), which reduced AAA development, ER stress, leukocyte infiltration, and senescence. Taken together, these data represent a unique signaling pathway whereby Ang II-induced mitochondrial fission contributes to disturbed proteostasis, culminating in VSMC senescence and vascular inflamm-aging. The elucidation of Ang II contribution to irreversible vascular senescence sheds light on potential alternative therapeutic targets for high-risk CVD populations.
Abstract P127: Serpinc1/Antithrombin III Attenuates Salt-Induced Hypertension
Authors: Wang Feng , Kong Yiwei , Li Junhui , Xue Hong , Liu Xuanchen , Usa Kristie , Geurts Aron M , Liang Mingyu
Published: September 2019

Antithrombin III (ATIII), encoded by the gene
Serpinc1
, is a serine protease inhibitor in the coagulation cascade and may inhibit inflammation and promote endothelial function.
Serpinc1
is down-regulated in Dahl salt-sensitive (SS) rats compared to several rat strains with reduced blood pressure salt-sensitivity. The aim of this study was to investigate the role and the potential therapeutic effect of
Serpinc1
/ATIII in salt-induced hypertension. ATIII activity was analyzed in patients with hypertension and the effect of
Serpinc1
knockout or overexpression was examined in rat models. For mechanistic analysis, inflammation and endothelial function were examined. Lower ATIII activity is associated with higher blood pressure levels in hypertensive patients (n=90, P=0.015). Hypertension grades are also negatively correlated with ATIII activity (Spearman's coefficient r
s
=-0.2779, P=0.008). Heterozygous knockout of
Serpinc1
in modestly salt-sensitive SS.13
BN26
rats exacerbated salt-induced hypertension (mean arterial pressure 141±5 mmHg in heterozygous knockout rats vs 128±2 mmHg in wild-type littermates after 14 days on a 4% NaCl diet, n=9 in heterozygous group and n= 10 in wild-type group, P<0.05).
Serpinc1
overexpression in SS rats using adeno-associated virus (AAV) attenuated salt-induced hypertension (mean arterial pressure 142±7 mmHg in SS rats treated with AAV-
Serpinc1
vs 189±13 mmHg in in SS rats treated with AAV-control after 14 days on a 4% NaCl diet, n=6 in AAV-
Serpinc1
group and n= 5 in AAV-control group, P<0.05). Mechanistically,
Serpinc1
insufficiency significantly increased renal outer medullary interleukin 6 mRNA and decreased endothelial nitric oxide synthase expression and endothelium-dependent vasodilation, while
Serpinc1
overexpression had the opposite effect. Treatment of
Serpinc1
heterozygous knockout rats with an interleukin 6 receptor antibody attenuated the exacerbation of salt-induced hypertension by
Serpinc1
insufficiency. In conclusion,
Serpinc1
/ATIII reduces inflammation, improves endothelial function, and attenuates salt-induced hypertension.
Abstract P129: White Coat Effect Causes Excessive Antihypertensive Treatment in Low Risk Patients
Authors: Duarte Mariano , Sarotto Lidia , Aquieri Analia , Coyle Javier , Scacchi Bernasconi Pablo , Reyes Toso Carlos
Published: September 2019

Office recording blood pressure (BP) gives at best a rough estimate of a person’s usual BP, and it is controversial that a few office BP determinations govern the diagnosis and treatment guidelines for hypertension. In this context it acquires importance the white coat effect (WCE), which is a significant fall in ambulatory BP compared with that measured in a clinical setting.Despite the introduction of ambulatory pressure, specially 24h BP monitoring (ABPM) has had a great impact on both the decision to treat or not a patient (P) with hypertension, it has not been considered either in fundamental studies such as the Sprint or in the diagnostic and treatment recent guidelines for hypertension.In our country, primary care physicians have taken new objectives of BP treatment very seriously based only on their office records.Hypertensive P with visión déficits, from the neuroophthalmology section of our hospital, are periodically referred to our Laboratory for screening of hypertension and vascular complications. In the last two years 62 P were evaluated.In low risk (LR) P, who do not have hypertensive target organ damage or chronic symptoms, we observed a temporal relationship between ocular symptoms and the start or increase of antihypertensive treatment So we decide to carry out a preliminary prospective study including LR hypertensive P between Sep 2017 to Mar 2019. P older than 80 and those who had secondary hypertension were excluded. All were studied with ABPM to compare ambulatory and office BP values, day and night time BP.BP was recorded when they were derived and in a subsequent visit a week later where the ambulatory monitor pressure was also placed.The results showed in LR group significantly higher office systolic (S) BP values (143±11 mm Hg) compared with ambulatory BP: 24h SBP 117±8 mm Hg (p<0.01), daytime SBP 120±9 mm Hg (p<0.01) and nigthtime SBP 94±8 mm Hg (p<0.01), and we observed WCE in 18 of 30 P (56%). Under estimating or not detecting WCE can lead to excessive antihypertensive treatment and cause ocular and other tissues hypoflux.

Conclusions:
In low risk P office BP values should be corroborated with ambulatory BP values, either systematic ambulatory monitoring or with 24 h ABPM before starting or before increasing the antihypertensive treatment.
Abstract P137: Immune Response Factors in Patients With Arterial Hypertension, Diabetes Mellitus and Acute Coronary Syndrome
Authors: Glova Svetlana , Shlyk Sergey , Khaisheva Larisa
Published: September 2019

Purpose:
To study cardiac remodeling in patients with arterial hypertension (AH) and acute coronary syndrome (ACS) complicated with diabetes mellitus (DM) through analysis of laboratory parameters and echocardiogram.

Methods:
A total of 67 patients were prospectively enrolled (age range: from 36 to 79 years; average: 60,96 ± 9,22 years) with AH and ACS who were admitted to Emergency Hospital. The patients were divided into 2 groups depending on the presence of DM: 23 patients with DM (age average: 65,09 ± 7,73 years) and 44 without DM (age average: 58,79 ± 9,19 years). Serum triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), high sensitive C reactive protein (hs-CRP), antibodies to LPS General Enterobacteriaceae, antibodies to LPS Re-Glycolipid were tested for all patients. Echocardiograms were obtained on all the patients, interventricular septal thickness (IVSd) and others parameters were measured by taking the mean values of three continuous heartbeat cycles in the expiratory state. All indicators were calculated using the statistics program Statistica, a P-value of < 0,05 was considered statistically significant.

Results:
There were no significant differences in the levels of serum hs-CRP, TC, HDL-C, LDL-C; but TG levels were significantly higher in patients with DM ( 3,16 ± 2,61 mmol/l) than in controls (1,75 ± 1,33 mmol/l, p<0,05). Serum antibodies to LPS General Enterobacteriaceae levels (441,52 ± 303,70 A.U.O.D) were also significantly higher in the DM group than in controls (271,41 ± 200,13 A.U.O.D, p<0,05). The levels of serum antibodies to LPS General Enterobacteriaceae were positively correlated with IVSd (r = 0,765, p<0,05).

Conclusion:
The data demonstrated, that patients with DM and AH have a greater immune response which correlates with indicators of left ventricular remodeling. The mechanism of the cardiac function impairment, however, has not been clearly explained yet. The role of the immune response in the development of cardiac muscle remodeling is not fully understood. It Is currently considered that these changes may participate in the pathological process of left ventricular remodeling in patients with AH and DM.
Abstract P146: Dopaminergic Stimulation Increases Gastrin Secretion via a PKA-PPAR-Alpha Pathway
Authors: Xu Peng , Gildea John J , Yue Wei , Jose Pedro A , Felder Robin A
Published: September 2019

Dietary sodium stimulates renal excretion of sodium long before the sodium is enterally absorbed. Moreover, intravenously administered sodium does not stimulate as large an excretory response as sodium taken by mouth. We previously showed that sodium stimulates an increase in gastrin mRNA and protein in stomach G-cells via PPAR-α and dopamine D1 receptor (D
1
R). Studies have shown that PKA pathway is important in the regulation of PPAR-α activity, and PKA is also involved in the D
1
R pathway. Thus, we hypothesized that D
1
R may regulate PPAR-α through PKA in human G-cells in response to sodium. Human G-cells were treated with 8-Br-cAMP, a cell-permeable second messenger analog, and Rp-cAMP (RPCA), a PKA inhibitor. Image analysis showed there was more PPAR-α in the nucleus with 8-Br-cAMP treatment, and less PPAR-α in the nucleus with RPCA treatment. Therefore, PKA is involved in regulating PPAR-α (VEH, 1194±74; 8-Br-cAMP, 1490±44; RPCA, 740±75; 8-Br-cAMP+ RPCA, 1037±54; VEH vs 8-Br-cAMP, P<0.01; 8-Br-cAMP vs 8-Br-cAMP+ RPCA, P<0.001; one-way ANOVA, n=13). Moreover, gastrin mRNA was increased by 8-Br-cAMP stimulation while the increase was blocked by RPCA (VEH, 1.01±0; 8-Br-cAMP, 1.32±0.07; RPCA, 0.82±0.08; 8-Br-cAMP+ RPCA, 0.9±0.05; VEH vs 8-Br-cAMP, P<0.05; 8-Br-cAMP vs 8-Br-cAMP+ RPCA, p<0.01; one-way ANOVA, n=3). Gastrin protein level was also increased by 8-Br-cAMP treatment with image analysis (VEH, 1.14±0.01; 8-Br-cAMP, 1.28±0.01; RPCA, 1.17±0.01; 8-Br-cAMP+ RPCA, 1.38±0.03; VEH vs 8-Br-cAMP, P<0.01; one-way ANOVA, n=3). These data indicate that PKA is involved in the D
1
R and PPAR-α pathways to regulate G-cell gastrin expression stimulated by sodium.