bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P285: Hydralazine Attenuates the Development of Hypertension in the Female Dahl Salt-sensitive Rat in a T Cell-independent Manner
Authors: Pai Amrita V , West Crystal A , Souza Aline , Kadam Parnika S , Pollner Emma J , West David A , Ji Hong , Wu Xie , Sandberg Kathryn
Published: July 2021

Introduction:
Several studies in Dahl salt-sensitive (
DS
) rats suggest that T cells play a role in salt-sensitive hypertension. To further investigate the role of T cells, we compared T cell profiles in hypertensive DS and normotensive Dahl salt-resistant (
DR
) rats as well as in DS rats treated with hydralazine (
HYD
) to attenuate the development of hypertension.

Methods:
Mean arterial pressure (
MAP
) was measured by telemetry in DS rats (n=13) from 1 to 4.5 months (
mo
) of age. At 1.5 mo, all of the DR (n=8) and half of the DS rats were treated with vehicle (VEH, n=7). The other half of the DS rats (n=6) received HYD (25 mg/kg/day) in the drinking water. At 4.5 mo, renal T helper (
Th
) and cytotoxic (
Tc
) cells were assessed by multicolor flow cytometry.

Results:
In the DS kidney, the frequency of CD4
+
Th cells [(%): DS-VEH, 76±1.2* vs. DR-VEH, 55±0.7; *p<0.0001; n=7-8/group] was higher while the frequency of CD8
+
Tc cells [(%): DS-VEH, 14±1.2* vs. DR-VEH, 35±1; *p<0.0001; n=7-8/group] was lower compared to DR rats. 10 weeks of HYD treatment attenuated the age-associated increase in MAP observed in DS rats [p<0.0001, Two-Way ANOVA (time, treatment); MAP (mmHg): DS-VEH, 157±4 vs. DS-HYD, 133±3; *p<0.0004; n=6-7/group]. HYD had no effect on the frequency of CD4
+
[(%):77±1.5] or CD8
+
[(%):15.5±0.9] T cells in the kidney of DS rats [(CD4
+
): DS-VEH vs. DS-HYD, p=0.83; (CD8
+
): DS-VEH vs. DS-HYD, p=0.5; n=7-8/group]. In summary, the ratio of Th (CD4
+
) to Tc (CD8
+
) cells is higher in the kidney of DS compared to DR rats and HYD had no effect on the T cell profile in the DS rat kidney under conditions in which the MAP was attenuated by 20 mm Hg.

Conclusions:
These findings indicate the DS rat has more active Th cells in the kidney compared to the DR rat. Our study also suggests that vasodilators can attenuate the development of hypertension in the DS rat in a Th- and Tc-independent manner.
Abstract P302: Nicotinamide Ameliorates IgA Nephropathy and Pregnancy Outcome in Pregnant Grouped-ddy Mice
Authors: Fushima Tomofumi , Sekimoto Akiyo , Oe Yuji , Sato Emiko , Sato Hiroshi , Ito Sadayoshi , Takahashi Nobuyuki
Published: July 2021

Objective:
IgA nephropathy (IgAN) affects women in childbearing ages. We have reported that nicotinamide (Nam) ameliorates a preeclampsia (PE)-like condition and pregnancy outcome in PE mouse models (
PNAS
2016, AJP 2017). Our preliminary data show that pregnant grouped ddY (gddY) mice, a model of IgAN, have PE-like phenotype and adverse pregnancy outcome. The aim of the present study is to clarify whether Nam ameliorates IgAN and pregnancy outcome in pregnant gddY mice.

Design and Method:
Pregnant gddY mice 9-11 weeks of age were divided into four groups (gddY, gddY+Nam, gddY+sFlt-1, and gddY+sFlt-1+Nam). PE-like phenotype was induced by administering sFlt-1 adenovirus (4x10
8
pfu) at 14.5 dpc. Nam 500 mg/kg/day was administered daily using gavage from 12.5 dpc. Age-matched pregnant slc:ddY mice were used as a control.

Results:
Compared with control ddY mice, gddY mice showed higher SBP and urinary albumin excretion (Fig. 1), and smaller litter size and fetal weights. Moreover, gddY+sFlt-1 mice showed severe endotheliosis and poor pregnancy outcome. Nam alleviated hypertension, albuminuria (Fig. 1), mesangial expansion and endotheliosis in gddY and gddY+sFlt-1 mice. In addition, Nam prolonged pregnancy period of gddy+sFlt-1 mice. Fetal weights from gddY+Nam mice, and gddY+sFlt-1+Nam mice were larger than those of gddY and gddY+sFlt-1 mice.

Conclusions:
Nam alleviated maternal hypertension, proteinuria and fetal growth restriction in pregnant gddY and gddY+sFlt-1 mice. Nam could help treat maternal IgAN with pregnancy and PE with IgAN.
Abstract P311: Intracellular Renin Angiotensin Aldosterone System inMesangial Cells Under the Stimulus of Aldosterone
Authors: Stoll Danielle , Yokota Rodrigo E , Aragão Danielle S , Casarini Dulce E
Published: July 2021

Mesangial cells (MCs) are a local target for aldosterone (aldo) action in the modulation of the renin angiotensin aldosterone system (RAAS).Its molecular mechanisms is far from clear, and are extremely important in understanding renal pathologies. We investigated if the effect of aldosterone stimulus in supra, physiological and sub physiological doses was able to modulate the intracrine human MCs RAAS. We performed viability assays, western blot, immunofluorescence, ACE and ACE2 activities. As a result, we have obtained that the ACE activity was increased after MCs treatment with aldosterone 1 and 10 nM when compared with 0.1nM after 72h. Previous cells treatment with spirolactone followed by aldo reduced ACE catalytic activity but not ACE2. ACE and ACE 2 expression increased after 72h of MCs treatment with aldo 10 nM. The immunofluorescence showed that ACE was overexpressed in MCs after 72h with 10nM aldosterone treatment being similar to control group, differing from the treatment with spirolactone + aldo stimulation that decreased ACE expression, internalized Angiotensin II and changed the AT1 receptor localization. The same treatment increased MAS receptor production in MCs after 72h of aldosterone treatment with 10, 1.0, 0.1 and 0.01nM , but not with spirolactone + aldo treatment that inhibited receptor synthesis. ACE2 was detected in cell nucleus with 24h of treatment with aldo and in cytoplasm after 72h, being reduced after the treatment with spirolactone+aldo. Ang 1-7 was localized at cell nucleus and in cytoplasm after treatment with aldo 24h and 72h, decreasing with spirolactone + aldo treatment. Immunofluorescence results demonstrated that MCs pre-treated with spironolactone decreased ACE, ACE2 and MAS receptor expression, and altered ANG II localization, suggesting that spironolactone acts on the mineralocorticoid receptor internalizing ANG II into the nucleus, probably by AT1 and AT2 receptors pathways. These results demonstrated that aldosterone can modulate the local RAAS in mesangial cells suggesting that its physiological concentrations are necessary for the feasibility of these cells while high doses are cytotoxic and altered the local system.
Abstract P326: Effects of D
1
R/AT
2
R Coupling on Aminopeptidase N (APN) in Human Renal Proximal Tubule Cells (RPTC)
Authors: Mallory Micah J , Gildea John J , Xu Peng , Felder Robin A
Published: July 2021

Dopamine receptor type 1 (D
1
R) and angiotensin receptor type 2 (AT
2
R) uncoupling from their intracellular second messengers are implicated in both salt sensitivity of blood pressure (SS) and hypertension. Angiotensin III (Ang III) and dopamine (DA) work cooperatively through binding to the interdependent D
1
R and AT
2
R to regulate renal sodium balance through autocrine signaling pathways. Aminopeptidase N (APN) is a renin-angiotensin system (RAS) enzyme localized in RPTC responsible for converting the natriuretic peptide AngIII into the anti-natriuretic agonist angiotensin IV (AngIV). The expression of APN (measured by a fluorescently labelled CD13 antibody) was investigated after increasing intracellular salt concentration with both the ionophore monensin (100 μM, 1hr.) and NaCl buffer solution (50 mmol/L, 1 hr.) in known G protein coupled (i22) and G protein uncoupled (i19) RPTC. Increasing intracellular sodium resulted in a more dramatic decrease in overall APN expression in uncoupled cells (i19 vehicle (VEH) 1.00 ± 0.03, Mon 0.87 ± 0.01 fold, n=3, p<0.05) compared to a slight decrease in coupled cells (i22 VEH 1.00 ± 0.01, NaCl 0.96 ± 0.01 fold, n=6, p<0.05). Two unknown coupling urine cell lines (RMC031-202 and RMC031-6) were evaluated alongside these known cells in an attempt to classify each as coupled or uncoupled. RMC031-202 replicated i22 (coupled) trends while RMC031-6 closely replicated i19 (uncoupled) data. Moreover, baseline APN expression comparison (normalized to i22) between the cell lines reveled a significantly elevated baseline for known and suspected uncoupled cells (i19 1.69 ± 0.047, RMC031-6 2.01 ± 0.004 fold over i22, n=3, p<0.05). Known (i22) and suspected (RMC031-202) normally coupled cells had equivalent baselines (p>0.05). An uncoupling defect may result in decreased APN regulation in RPTC causing higher baseline levels of APN expression. These increased levels of APN, in turn, lead not only to amplified production of the anti-natriuretic agonist AngIV but also reduced potential for cooperative natriuretic AngIII/DA autocrine signaling thus disrupting the dopaminergic system’s ability to suppress RAS and maintain proper sodium balance.
Abstract P335: Greater Reduction in Sympathetic Tone following ET
B
Receptor Blockade in Rats Lacking the Clock Gene Bmal1 during High Salt Diet
Authors: Johnston Jermaine G , Becker Bryan K , Jin Chunhua , Pollock David M
Published: July 2021

The absence of diurnal oscillations in blood pressure is associated with increased cardiovascular morbidity and mortality. The clock gene
Bmal1
plays important roles in diurnal cardiovascular control as mice lacking
Bmal1
have lower blood pressure and lack a diurnal rhythm. Our lab has previously reported a global
Bmal1
knockout rat model that lacks a night-day difference in sodium excretion. Due to the importance of endothelin signaling in sodium homeostasis and autonomic tone, we sought to characterize the hemodynamic and autonomic responses of our
Bmal1
knockout (KO) rat to high salt diet and endothelin receptor blockade. Male rats homozygous for the
Bmal1
mutation (KO, n = 4) and wild type (WT, n = 7) littermate controls were implanted with telemetry transmitters to record blood pressure. After a recovery period of at least one week, the rats were placed on 7 days each of normal salt (0.49% NaCl) diet, high salt (4.0% NaCl) diet, followed by high salt diet containing the specific ET
B
receptor antagonist A192621 (10 mg/kg/day, p.o.). Rats were placed in metabolic cages for the last three days of each diet. Surprisingly, KO rats had a similar night-day difference in mean arterial pressure (MAP) as WT during normal salt diet (6.3 ± 0.4 vs. 6.9 ± 0.9 mmHg; respectively), high salt diet (7.1 ± 0.1 vs. 5.4 ± 0.9 mmHg; respectively), and high salt + A192621 (5.4 ± 0.4 vs. 4.8 ± 1.1 mmHg; respectively). KO and WT rats had similar 24-hr MAP during normal salt diet (104.1 ± 3.3 vs. 107.3 ± 1.2 mmHg; respectively), high salt diet (113.8 ± 4.1 vs. 114.0 ± 1.4 mmHg; respectively), and high salt + A192621 (136.3 ± 8.6 vs. 133.4 ± 3.1 mmHg; respectively). Despite these similar blood pressure responses to high salt diet and ET
B
antagonism, KO rats had a significantly greater reduction in vasomotor sympathetic to parasympathetic tone compared to WT rats as demonstrated by low frequency to high frequency (LF/HF) analysis of diastolic blood pressure variability (-0.9 ± 0.3 vs. 0.1 ± 0.2 ΔLF/HF relative to normal salt; respectively; p = 0.01). These results indicate that lack of
Bmal1
may result in greater ET
B
receptor mediated vasomotor sympathetic tone in rats fed a high salt diet and that factors other than
Bmal1
may be influential in circadian control of blood pressure in rats.
Abstract P339: Genetically Induced Renal Lymphangiogenesis Prevents the Development of L-NAME Hypertension in Mice
Authors: Lopez Gelston Catalina A , Balasubbramanian Dakshnapriya , Abouelkheir Gabriella R , Lopez Alexandra H , Hudson Kayla R , Johnson Eric R , Garza Victoria C , Daboul Reem A , Rutkowski Joseph M , Mitchell Brett M
Published: July 2021

In humans and experimental animals, persistent immune system activation, accumulation of immune cells in the kidney, and subsequent inflammation plays an essential role in the development of hypertension (HTN). To reduce inflammation, lymphatic vessels drain extracellular fluid from the interstitium and traffic immune cells to draining lymph nodes. However, little is known about the connection between hypertension and renal lymphatic vessels. We hypothesized that renal lymphatic vessel density would increase in mice with L-NAME HTN and that genetically induced renal lymphangiogenesis would prevent this increase in blood pressure. L-NAME (0.5 mg/mL) was administered in the drinking water for two weeks and caused HTN (SBP: 153±3 vs. 103±3 mmHg; p<0.05) and renal lymphatic vessel dilation compared to control mice. Kidneys from mice with L-NAME HTN had significantly increased gene expression of the lymphangiogenic marker
Vegfc
, macrophage marker
Adgre1
(F4/80), dendritic cell marker
Cd11c
, Th1 cell marker
Tbx21
, and the pro-inflammatory cytokine
Il6
. Blood pressure decreased after a two-week washout period following L-NAME (SBP: 113±2 mmHg) which was associated with a decrease in renal gene expression of
Adgre1
(F4/80) and
Cd11c
, however renal lymphatic vessels remained dilated. To determine if augmenting renal lymphatic vessel density prior to L-NAME treatment would prevent HTN, we used transgenic mice that in response to doxycycline undergo kidney-specific VEGF-D overexpression (KidVD+ mice) and renal lymphangiogenesis. Doxycycline (200 mg/L) was administered in the drinking water of KidVD+ and KidVD- mice for four weeks with L-NAME being added during the final three weeks. Starting doxycycline one week prior to L-NAME prevented HTN in KidVD+ mice while slightly decreasing SBP in KidVD- mice (SBP: 112±4 vs. 134±2 mmHg; p<0.05). Renal gene expression of the Th17 cell marker
Rorc
was decreased and the lymphatic chemokine markers
Ccl21
and
Ccl19
were increased significantly in KidVD+ mice. These data together demonstrate that L-NAME HTN can alter the size of renal lymphatic vessels and genetically augmenting renal lymphatic vessel density prior to L-NAME can prevent the development of HTN.
Abstract P340: Immunomodulatory Effect of Rapamycin on the Expression of Anti-inflammatory Cytokines in Npr1 Gene-deleted Mice
Authors: Gogulamudi Venkateswara R , Subramanian Umadevi , Bloodworth Meaghan , Pandey Kailash N
Published: July 2021

Disruption of natriuretic peptide receptor-A (NPRA) gene (
Npr1
) activates the pro-inflammatory responses, which contributes to the pathogenesis of hypertension and end-organ damage. The objective of this study was to determine the kinetic responses of pro- and anti-inflammatory cytokines in
Npr1
gene-knockout (KO) mice.
Npr1
0-copy (

Npr1
-/-

), 1-copy (

Npr1
+/-

), and 2-copy (
Npr1
+/+
) mice were pre-treated with rapamycin and multiplex analyses were done to assess cytokines levels. Pro-inflammatory cytokine, IFN-γ protein levels in plasma and kidney of 0-copy and 1-copy mice were markedly higher compared with 2-copy mice (76±1; 49±2 vs 32±1.3 pg/ml; 79±2; 29±1 vs. 27±0.5 pg/mg, respectively). Similarly, IL-6 levels in plasma and kidney were significantly elevated in 0-copy and 1-copy mice than 2-copy mice (52±1; 27±0.5 vs.12±0.4 pg/ml; 49±1.5; 38±2 vs.18±1.1 pg/mg, respectively). Interestingly, anti-inflammatory cytokine IL-5 protein levels in plasma and kidneys were significantly down-regulated in 0-copy and 1-copy mice than 2-copy mice (6±0.8; 5±0.1 vs. 12±0.5 pg/ml; 6±0.6; 9±0.4 vs. 28±0.5 pg/mg). IL-10 levels in plasma and kidney of 0-copy and 1-copy mice were also significantly decreased than 2-copy mice (22±0.4; 39±1 vs. 62±3 pg/ml; 14±1.7; 36±0.2 vs. 52±3 pg/mg). Rapamycin significantly reduced the levels of IFN- γ in plasma and kidney of 0-copy (50%, 35%) and 1-copy (63%, 55%) mice and IL-6 level in 0-copy (60%, 38%) and in 1-copy (40%, 26%) mice compared with 2-copy mice. In contrast, rapamycin treatment significantly elevated IL-5 levels in plasma and kidneys of 0-copy (68%, 77%) and 1-copy (61%, 64%) mice and IL-10 levels in 0-copy (80%, 78%) and 1-copy (47%, 25%) mice than 2-copy mice. A significant decrease in blood pressure occurred in rapamycin-treated 0-copy (19±4 mmHg) and 1-copy (12±3 mmHg) mice than untreated control mice. The results demonstrate that the expression of pro-inflammatory cytokines is greatly upregulated in
Npr1
KO mice compared with 2-copy mice and rapamycin serves as the immune modulator of anti-inflammatory cytokines in these animals. The present findings implicate that rapamycin might act as an anti-inflammatory drug for the treatment of pathophysiology of hypertension-associated inflammation.
Abstract P345: Overexpression of Mitochondrial Deacetylase Sirt3 Protects Endothelial Function and Attenuates Hypertension While Sirt3 Depletion Increases Oxidative Stress and Endothelial Dysfunction Due to SOD2 Hyperacetylation
Authors: Dikalova Anna E , Itani Hana A , Pandey Arvind K , Harrison David G , Dikalov Sergey I
Published: July 2021

We have recently reported SOD2 hyperacetylation and reduced Sirt3 level in human subjects with essential hypertension. We hypothesized that diminished Sirt3 expression promotes endothelial dysfunction and hypertension while Sirt3 overexpression protects endothelial function and attenuates hypertension. Indeed, hypertension was markedly increased in Sirt3 knockout (Sirt3
-/-
) in response to angiotensin II (0.7 mg/kg/day) compared with wild-type C57Bl/6J mice. Sirt3 depletion caused SOD2 inactivation due to SOD2 hyperacetylation, increased mitochondrial O
2

•

and diminished endothelial nitric oxide. Angiotensin II infusion in wild-type mice was associated with Sirt3 inactivation and SOD2 hyperacetylation in aorta and kidney. To test the specific role of Sirt3 in vasculature we have generated tamoxifen-inducible endothelium specific Sirt3 knockout mice (Ec
Sirt3 KO
) and tamoxifen-inducible smooth muscle specific Sirt3 knockout mice (Smc
Sirt3 KO
). Deletion of Sirt3 in smooth muscle exacerbated hypertension (165 mm Hg vs 155 mm Hg in wild-type) and significantly increased mortality in angiotensin II infused Smc
Sirt3 KO
mice (30% vs 3% in wild-type) which was associated with higher rate of aortic aneurysm. Ec
Sirt3 KO
mice had elevated basal blood pressure by 12 mm Hg and hypertension was exacerbated in Ec
Sirt3 KO
mice accompanied by impaired vascular relaxation and reduced endothelial nitric oxide. Treatment of angiotensin II-infused Sirt3
-/-
mice with SOD2 mimetic mitoTEMPO rescued endothelial-dependent relaxation and reduced blood pressure. We tested if Sirt3 overexpression protects endothelial function and attenuates angiotensin II-induced hypertension. These new mice were obtained by crossing the EIIa-cre with Sirt3flox mice resulting in constitutively increased Sirt3 in the whole body. Sirt3 overexpression abolished angiotensin II induced impairment of vasorelaxation and attenuated development of hypertension. Our data suggest that diminished Sirt3 activity leads to SOD2 hyperacetylation and contributes to the pathogenesis of hypertension. It is conceivable that Sirt3 agonists and SOD2 mimetics may have therapeutic potential in cardiovascular disease.
Abstract P354: Left Ventricular Mass and Exagerated Hypertensive Blood Pressure Response to Bruce Exercise Stress Test in Diabetics and Nondiabetics
Authors: Balderas Michael , Cigarroa Joaquin , Lozano Daniel , Hecht Joan , Oliveros Rene A
Published: July 2021

The aim of or study was to see if an exaggerated BP response during the Bruce exercise test could differentiated target organ damage (TOD) in a population of diabetics v/s nondiabetic pts . We studied 105 pts for the performance of a stress test because of chest pain whose systolic BP rose 50mmHg or more at their peak exercise compared to their resting BP. There were 45 diabetics pts (DM) and 60 nondiabetic pts (NDM) pts. All pts were hypertensive on medication but their beta blocker medication was on hold for the performance of the stress test. The echocardiograms were performed using a Phillips IE 33 echo machine and the LV mass was calculated using the Deveraux formula using single plane views.

The was no statistical difference between both groups with respect to age, BMI and systolic and diastolic BP’s during rest and exercise. The HR at rest was not different between both groups but the HR at peak exercise was significantly higher for NDM compared to DM (p < 0.016). The LVMI was significantly higher in DM compared to NDM pts ( p = 0.04).

In conclusion, an elevated LVMI which is evidence for hypertensive target organ damage should be suspected in hypertensive pts who have an exaggerated BP response to the exercise Bruce stress test.

The reason for a significantly higher HR at peak exercise for NDM patients compared to DM pts may be related to better physical performance and therefore longer duration of exercise. Other possibilities will be discussed.
Abstract P359: Achieving Normal Blood Pressure with Cloud-based Monitoring and Management
Authors: Sanchez Jorge , Shams Tanzid , Fonner Clifford , Shah Nirav
Published: July 2021

Introduction:
We assessed the feasibility and impact of remote monitoring and medication management on hypertension control in a nursing home.

Hypothesis:
Uncontrolled hypertension is a causal factor for cardiovascular disease. We hypothesized that increased sensitivity to elevated blood pressure (BP) readings via remote monitoring and targeted medication management alerts would lead to higher rates of controlled hypertension.

Methods:
We followed 48 long-term nursing home patients (average age=68.4) over a 10-week period, of whom 21 were identified as uncontrolled hypertension with a reading >140/90 mmHg. BP readings were taken 3 times a week as compared to a norm of 1 measurement per 3 weeks. Blood pressure data was stored in a cloud and analyzed via algorithms. The physician was given a summary of data identifying those patients who met criteria for elevated BP with averaged per week mean systolic and diastolic blood pressure. Furthermore, patients were further stratified via an algorithm where systolic BP over 140 mmHg was reported as a fraction of the week with uncontrolled hypertension. Together these 3 variables guided the physician in making a determination of a decision to escalate pharmacologic therapy.

Results:
After monitoring and interventions there were significant decreases in the patients’ average BP (130.6 mmHg vs. 135.6 mmHg, p=0.027). Neurological (headache, vision changes) and cardiac symptoms (chest pain) were resolved or improved in 83% of patients (5 of 6). By end of the pilot 4.2% (2 of 48) remained hypertensive as compared to the initial 43.8% (21 of 48) found to be hypertensive at start of pilot; 95.8% (46 of 48) remained controlled by end of study. Furthermore, when compared with a similar cohort of patients, hospital admissions were 80% (2 versus 10) fewer in the study population.

Conclusions:
In agreement with our hypothesis, more frequent BP measurements and medication adjustments led to increased rates of hypertension control. We believe that normotension is achievable using cloud-based monitoring, reporting, and treatment. In conclusion, this new method requires serious consideration versus the current standard of care and could help provide improvements in skilled nursing facilities and other care settings.
Abstract P367: Masked Hypertension is Not Associated With Orthostatic Hypertension
Authors: Cigarroa Joaquin , Balderas Michael , Baez Christopher , Garza Benjamin , Hecht Joan , Oliveros Rene A , Chilton Robert
Published: July 2021

The aim of this study was to see if there is any association between masked hypertension (MHTN) and orthostatic HTN (OHTN). In addition, we evaluated if MHTN was associated with diabetes (DM). Lastly we compared BP and HR changes between DM and non-diabetics (NDM)pts.

We performed ambulatory BP monitoring (ABPM) in 70 consecutive pts referred to us for evaluation of hypertension. From this number of pts there were 20 pts with OHTN for an incidence of 28%. There were 8 pts with MHTN for an incidence of 11.4%. There were 26 pts with DM and 44 pts were NDM

The studies were performed after 5 minutes of rest. We obtained BP’s in the dominant arm. We subsequently performed the 24hs ABPM using Space Lab On Trak 90227 monitors.

Out of 8pts with MHTN, none had OHTN and only 2 were pts with DM. In addition, we compared age, weight, BP sitting and standing as well as HR sitting and standing in our 70 patients that were divided in 2 groups, DM v/s NDM. The following table depicted our results:

In summary, we found a higher sitting diastolic BP in nondiabetic pts. There was no significant difference between both groups in the remaining parameters.

In conclusion, in our small population of pts there was no association between MHTN and OHTN. The association between MHTN and DM was very low. When comparing 8 different parameters depicted in the table the only significant difference between DM and NDM was on the sitting diastolic BP.
Abstract P376: Impact of Selected Differences Between Automated versus Conventional Office Blood Pressure and Adherence on the Prevalence of SPRINT Eligibility in Korean Population
Authors: Shin Jinho , Choi Sung-Il , Park Sungha , Sung Ki Chul , Kim Kwang-il , Ihm Sang Hyun , Pyun Wook Bum , Kim Soon Kil
Published: July 2021

Background:
For the applicability of Systolic Blood Pressure (BP) Intervention Trial (SPRINT) is controversial due to regional cardiovascular (CV) risk stratification system, AHM adherence, and the automated office BP (AOBP) methodology.

Method:
General population aged 30 or more (n=205282) and 55208 hypertension subject in Korean National Health Insurance Service - National Sample Cohort (NHIS-NSC) 2010 data were analyzed. Three BP criteria 1, 2, and 3 according to the selected difference between office BP and AOBP of 0 mmHg, 5 mmHg, and 10 mmHg, respectively. Also according to the risk groups and adherence status, prevalence of SPRINT eligible subjects were investigated.

Results:
SPRINT eligibility subjects were observed in 6.5[6.4~6.7]% vs 5.6[5.5~5.7]% in the general population 15.9[15.7~16.0]% vs 14.8[14.7~15.0]% in hypertension patients by KSH vs. FRS, respectively ([ ], 95% confidence interval). According to BP criteria 1 to 3, SPRINT eligibilities by KSH were different significantly in the general population (6.5[6.4~6.7]%, 4.0[3.9~4.1]%, and 2.7[2.6~2.7]%, respectively) and in hypertension patients (15.9[15.7~16.0]%, 11.8[11.7~12.0]%, and 9.9[9.8~10.0]%, respectively). When the SPRINT eligibility was allowed only in PDC >= 300 days per year in hypertension patients, the prevalence according to the BP criteria 1 to 3 were 8.0[7.7~8.2]%, 5.4[4.3~4.7]%, and 4.1[3.9~4.2]%, respectively by KSH and 8.1[7.8~8.3]%, 5.7[5.5~5.9]%, and 4.4[4.3~4.6]%, respectively by FRS.

Conclusion:
SPRINT eligibility can be markedly differed not by the risk stratification systems but by the application of AOBP to conventional office BP and adherence.
Abstract P379: Patient and Caregiver Experiences With the Diagnosis of Neurogenic Orthostatic Hypotension
Authors: Hewitt Lawrence A , Adler Charles H , Claassen Daniel O , Gibbons Christopher H , Raj Satish R
Published: July 2021

Objective:
To understand the challenges to diagnosis in patients with neurogenic orthostatic hypotension (nOH)

Background:
nOH is a sustained reduction in blood pressure (BP) with postural change associated with autonomic dysfunction. Despite symptoms of nOH, many patients struggle to find an accurate diagnosis.

Methods:
An online, US-based survey designed by the authors was conducted by Harris Poll. Eligible participants were ≥18 years of age with Parkinson disease, multiple system atrophy, or pure autonomic failure and ≥1 of the following: orthostatic hypotension (OH), nOH, low BP, OH/nOH symptoms, or were caregivers of eligible participants.

Results:
The survey included 363 patients and 128 caregivers. Groups were separate, where caregivers were not the caregivers to patient responders. Respondents indicated that patients experienced nOH symptoms long term
(Table 1)
. Most patients (69%) and caregivers (59%) reported discussing nOH symptoms with a healthcare provider (HCP) within the first year of symptom onset, but only 36% of patients and 16% of caregivers reported a formal diagnosis of OH or nOH. Of those with a formal diagnosis, the majority of patients (50%) were frustrated by the path to diagnosis and more than 40% of patients and caregivers reported that the patient saw ≥3 HCPs before diagnosis. After diagnosis, most patients (70%) and caregivers (60%) reported improved symptom management.

Conclusions:
This survey reveals that patients and caregivers may find the path to nOH diagnosis challenging and suggests increased awareness among HCPs is needed. Once a diagnosis is made nOH symptoms are better managed.
Abstract P382: Management and Treatment of Neurogenic Orthostatic Hypotension: Results From a Survey of Patients and Caregivers
Authors: Hewitt Lawrence A , Adler Charles H , Claassen Daniel O , Gibbons Christopher H , Raj Satish R
Published: July 2021

Objective:
To understand the patient and caregiver experience with the management of neurogenic orthostatic hypotension (nOH)

Background:
nOH is a sustained reduction in blood pressure (BP) with postural change associated with autonomic dysfunction. Clinical symptoms may include falls, leading to activity limits and a diminished sense of well-being.

Methods:
A US-based survey designed by the authors was conducted by Harris Poll. Eligible participants had Parkinson disease (PD), multiple system atrophy, or pure autonomic failure and ≥1 of the following: orthostatic hypotension (OH), nOH, low BP, OH/nOH symptoms, or were caregivers of eligible patients. Descriptive statistics are reported.

Results:
PD was the most frequent underlying diagnosis
(Table 1)
. Healthcare provider (HCP) communication with patients was rated as satisfactory by ≥75% of respondents, yet when nOH symptoms were first discussed with the HCP, only 35% of patients and 31% of caregivers reported the patient received guidance on management. The most frequently recommended interventions are listed in
Table 1
; 25% of patients reported that no interventions were recommended. Medication prescribed to treat nOH was reported by 34% of patients and 45% of caregivers. Among patients treated, 79% of patients and 71% of caregivers said that the patient’s symptoms were somewhat to very well managed.

Conclusions:
Survey findings suggest the need for increased awareness of nOH and engagement with patients and caregivers regarding symptom management. A variety of interventions were recommended; no single treatment approach was noted. Respondents felt nOH symptoms were at least somewhat well managed with treatment.
Abstract P385: Switching Insufficient Hypotensive Monotherapy to ARB/CCB Combination Tablet in Elderly Patients Increases Both Patient and Physician Satisfaction Rates and Contributes Better Patient-physician Concordance (Patients Voice study)
Authors: Ikeda Yoshiyuki
Published: July 2021

Aim:
This study was conducted to evaluate the effect of ARB/CCB combination tablet treatment considering patient-physician concordance on the patient and physician satisfaction for the hypertensive treatment.

Methods:
In an open-label, multicenter study, patients with insufficient hypotensive effect receiving treatment with ARB or CCB monotherapy were enrolled and their medication switched to an ARB/CCB combination tablet taken for 12 weeks. Home and clinic BP rates were evaluated at baseline and at 12 weeks. Both physicians and patients participated in satisfaction surveys concerning the treatment at baseline and at 12 weeks.

Results:
One hundred twelve patients were screened and 85 patients were enrolled. Significant differences were found between patient and physician rates of satisfaction and dissatisfaction in most survey items at baseline. Both home and clinic BP rates showed a significant decrease after switching to the ARB/CCB combination tablet. Patient satisfaction increased for the following survey items: treatment, 69.4% (59/85) to 90.1% (73/81); antihypertensive drugs, 60.0% (51/85) to 76.5% (62/81); clinic BP, 37.0% (31/84) to 68.8% (55/80); and home BP, 41.2% (35/85) to 67.5% (54/80). Component ratios of both patient and physician satisfaction showed significant increases in the following survey items: satisfaction with treatment, 18.8% (16/85) to 65.4% (53/81); involvement in treatment, 44.7% (38/85) to 65.4% (53/81); antihypertensive drugs, 18.8% (16/85) to 55.6% (45/81); clinic BP, 10.7% (9/84) to 46.3% (37/80); and home BP, 9.5% (8/84) to 46.3% (37/80). Our results indicate that, together with the effectiveness of the ARC/CCB combination tablet, participation in a satisfaction survey and access to a home BP monitor may have contributed to an increase in patient involvement in their treatment, a more mutual relationship between patients and physicians, and improvement in patient satisfaction.

Conclusion:
After switching to a ARB/CCB combination tablet treatment, better control of BP was found in patients with insufficient hypotensive effect from ARB or CCB monotherapy. Surveys showed that satisfaction rate for patients and physicians were improved in addition to patient-physician concordance.
Abstract P393: Orthostatic Heart Rate-Blood Pressure Relationship Identifies Neurogenic Orthostatic Hypotension
Authors: Velasco Alejandro , Okamoto Luis E , Garland Emily M , Yu Chang , Biaggioni Italo
Published: July 2021

Background:
Neurogenic orthostatic hypotension (nOH) is a chronic disabling condition associated with significant morbidity and mortality. Currently, the diagnosis of nOH relies on impaired autonomic reflexes as determined by testing available only in specialized centers. Our objective was to test the hypothesis that a blunted heart rate (HR) increase in response to a given systolic blood pressure (SBP) fall will correctly diagnose nOH.

Methods:
We performed a retrospective study of nOH patients (studied in an inpatient environment off medications that can interfere with autonomic function) and control subjects. nOH was diagnosed on the basis of SBP fall ≥20 mmHg on standing associated with a decrease in SBP≥ 20 mmHg during phase 2 of the Valsalva maneuver and absence of phase 4 SBP overshoot. Controls had any SBP fall on standing but intact autonomic reflexes. Receiver operator characteristic curve (ROC) analysis was performed on the ratio of the changes from supine to 3 min standing in HR and SBP (ΔHR/ΔSBP).

Results:
We studied 171 nOH patients (66±1 years, males 61%, multiple system atrophy 42%, Parkinson disease 14%, pure autonomic failure 32% and undetermined 12%) and 53 controls (51±3 years, males 28%). nOH patients had a greater drop in standing SBP (-63±2 vs. -16±4 mmHg in controls; p<0.01) but a smaller increase in HR (13±1 vs. 18±1 bpm in controls; p<0.01). The ROC analysis at 95% Confidence Interval showed that a ΔHR/ΔSBP ratio <0.445 had a 81% specificity and 79% sensitivity in identifying nOH (AUC=0.86, p<0.01. Figure).

Conclusions:
Our study suggests that a simple ratio of ΔSBP/ΔHR <0.445 during a posture test in clinic can reliably identify patients with nOH.
Abstract P396: The Stroke Belt: Forged in the Heat of the Buckle? A Hypothesis
Authors: Grim Clarence
Published: July 2021

The “stroke belt”(SB) in the SE USA has significantly higher stroke rates in whites (W) and African Americans (AA). HTN is the major driving force. The “Buckle” (B) of the SB, with even higher rates, lies along the costal “low country” plains of the Carolinas. Being born in the B is a powerful exposure that increases risk. Forty percent of all US slaves came thru, slaved and many died in the B of the SB. While reading the scholarly review “Slavery, Disease and Suffering in the Southern Low Country”, by Dr. Peter McCandless, (Cambridge U Press, 2011) I was stuck with the effect of the hot, humid weather with morbidity and mortality in the B. He details three decimating “fevers”. The first two, Malaria and Yellow Fever, are known to have left their mark on the human genome. The third fever, “Malignant Fever” (MF), coined by James Lind in “An Essay on Diseases Incidental to Europeans in Hot Climates” (London, 1768). MF was characterized as a fever of sudden onset resulting in rapid death in a few days. Lind describes MF morality in sailors “wooding” onshore during hot days who died overnight if they failed to return to the “cleaner air” of the ship. Many new arrivals, including military forces, to the SB/B succumbed to MF in days. Especially in the summer. Treatment of MF was removal to an area of “healthier air”/high country which quickly “cured” MF. I suggest this lowered the heat index, improving survival in heat illness/stroke or “Malignant fever”. In addition, an affliction called the “Dry Agues” characterized by muscle spasms, weakness and physical and mental fatigue was a major cause of disability during the summer. I interpret this as the classic features of hypokalemia driven by Na/K losses during heat adaptation and modulated by intakes of Na, K and the RAAS. As death from terminal heat stoke manifests as yellow skin/bleeding diathesis many of these deaths were likely wrongly attributed to Yellow Fever. Recent US military research documents a lower susceptibility to heat injury in both Ws and AAs from the SB/B. As the genes sing the songs of survival, I propose that selective survival, related to heat illnesses, plays a role in today’s greater prevalence of HTN in Ws and AAs in the SB and its B. Study of family trees, their genes and the physiology of heat control systems should be informative.
Abstract P399: The Association of Serum Aldosterone with Sex, Age, and Sodium Status
Authors: Rao Ajay D , Zhao Huaqing , Vasan Ramachandran S , Adlin E V
Published: July 2021

Primary aldosteronism (PA) is now recognized as the most common cause of secondary hypertension. Although the aldosterone-to-renin ratio is recommended for case detection, screening rates for PA remain low. Based on our prior study in low-renin hypertension, we hypothesized that a statistical adjustment for age, sex, and sodium status would improve the diagnostic accuracy of aldosterone measurements.

Data from the cohort of 3,345 individuals in the sixth examination cycle of the Framingham Offspring Study was analyzed. In addition to the standard study protocol, blood was drawn for later measurement of aldosterone. After exclusions, the final analysis consisted of 1,468 normotensives (652 men and 834 women), aged 29 to 85. To compare levels of continuous variables in two groups, we used independent samples t tests. We regressed natural-log-transformed values of aldosterone on age, sex, and the urine sodium/creatinine ratio. Unimodality of aldosterone (adjusted and unadjusted) was tested utilizing dotplots and the dip test.

The mean aldosterone levels were 10.4 ± 5.89 ng/dL in women and 11.3 ± 6.14 ng/dL in men (p < 0.005). Age, sex, and urine sodium/creatinine ratio were each significantly associated with aldosterone (p < 0.005). The proportion of variability explained by age, sex, and urine sodium/creatinine was 0.91%,1.3%, and 8%, respectively. The fully adjusted model r
2
= 0.0948. When adjusted for age, sex, and urine sodium/creatinine ratio, the distribution of aldosterone was unimodal (dip test: 2.26 ± 0.17 ng/dL, p = 0.9973); when unadjusted, the distribution of aldosterone was not unimodal (dip test, p ≤ 0.005). The dotplot and Q-Q plot showed a normal distribution of aldosterone after adjustment.

In this large, community-based population, adjustment for age, sex, and sodium status resulted in a more normal distribution of aldosterone. PA has been described as a condition “in which aldosterone production is inappropriately high for sodium status.” Our study suggests that appropriate adjustment of the measured serum aldosterone concentration may provide a more accurate approximation of the renin-angiotensin aldosterone system. Studies in populations of PA are needed to test for improved diagnostic accuracy that may result from this adjustment.
Abstract P422: Two-kidney One Clip (2k1c) Hypertension Reduces Complexity of Heart Rate Variability in Mice
Authors: Rodrigues Fernanda L , Silva Luiz E , Silva Carlos A , Carneiro Fernando S , Tostes Rita C , Fazan Rubens , Salgado Helio C
Published: July 2021

Introduction:
Hypertension is the most common chronic cardiovascular disease, being multifactorial in origin and an important cause of morbidity and mortality worldwide. Complex behaviors of heart rate series have been widely recognized and the loss of complexity in heart rate variability (HRV) has been shown to predict adverse cardiovascular outcomes. We hypothesized that two-kidney one clip (2K1C) hypertension reduces the HRV complexity in mice.

Methods and Results:
C57BL/6 mice were anesthetized with isoflurane and submitted to 2K1C hypertension by placing a silver clip (0.12 mm) around left renal artery. After 4 weeks, mice were implanted with subcutaneous electrocardiogram (ECG) electrodes and allowed to recover for 48 h. On the day of the experiment, the ECG was recorded for 30 minutes in conscious, unrestrained mice. At the end of the recording, arterial pressure (AP) was directly measured in each mouse under isoflurane anesthesia. RR interval time series were generated and the complexity of HRV was determined using detrending fluctuation analysis (DFA) and multiscale entropy (MSE). Mean AP was higher in 2K1C mice (133±2 vs 93±4 mmHg) while the HR was similar between groups. DFA scaling exponents were calculated in short (5 to 15), mid (30 to 200) and long (200 to 1500) window sizes, but only the long-term exponent was different between groups (1.27±0.09 vs 0.89±0.08 in 2K1C and sham mice, respectively). MSE was calculated up to scale 20 and averaged in short (1 to 5) and long (6 to 20) time scales. In both short (0.75±0.16 vs 1.25±0.11) and long (0.76±0.17 vs 1.22±0.09) ranges, entropy is lower in hypertensive mice.

Conclusions:
The complexity of HRV dynamics was found lower in renovascular hypertensive mice. Both sympathetic and vagal control of the heart seems to be involved in this process, as predictability (MSE) and fractality (DFA) is affected in various temporal scales. Nevertheless, the greatest entropy difference between groups is found at scale 6, which is closely related to respiration.
Abstract P439: Fibromuscular Dysplasia Of The Iliac And Renal Arteries: A Rare Case Report And Literature Review
Authors: Fan Luyun , Ma Wenjun , Zhang Huimin , Cai Jun
Published: July 2021

Background:
Iliac arterial fibromuscular dysplasia (FMD) is an orphan type of FMD, a non-atherosclerotic non-inflammatory arteriopathy predominantly among women aging from 20 to 60. The demographic, clinical features and therapeutic algorithm of iliac arterial FMD have not been precisely described.

Patient Concerns:
A 31-year-old Chinese male was referred for 3-month-ago onset hypertension, low serum potassium, and small-sized right kidney with normal renal artery under ultrasound examination. Spirolactone was poorly effective in this patient.

Diagnosis:
Contrast-enhanced computed tomographic angiography (CTA) and three-dimensional reconstruction of the whole aorta discovered an aneurysm from right common iliac artery (CIA) to the internal iliac artery, consistent with left CIA dissection and a remarkable right renal artery aneurysm before a stenosis, which was then confirmed through digital subtraction angiography.

Intervention:
Percutaneous transluminal angioplasty (PTA) of right renal artery was operated and a stent was deployed in left CIA.

Outcome:
This patient was normotensive, asymptomatic and free from recurrence without any antihypertensive agents at an 8-month follow-up.

Conclusions:
A total of 111 iliac arterial FMD cases (female, 84.7%; median age, 52±12.8 years) have been reported. Asymptomatic condition (49.5%) and claudication (40.5%) consist the majority of clinical presentations. Bruit (64.9%) and pulse deficits (39.4%) are the most popular signs. External iliac artery involved is approximate threefold of common and internal iliac arteries, usually accompanied with renal artery (71.2%, presenting hypertension) or carotid artery involvement (50.5%). A system screening among iliac or renal arterial FMD patients is therefore suggested with CTA from neck to pelvis and MRA in head. Dissection accounts for 15.3% cases, usually presenting ischemia symptoms with an inclination to young males. Conservative medication is efficient among 61.3% patients and PTA was operated in 15 patients with satisfactory outcomes in 86.7%. Stenting is an optimal recommendation of iliac artery FMD with progressive dissection. PTA is the first choice of short-duration renovascular hypertension due to FMD especially in young patient.
Abstract P447: Hesperidin, Ingredient of Citrus Fruits Juice, Attenuates Cognitive Impairment Induced by Ischemic Brain Damage
Authors: Kawakami Moe , Iwanami Jun , Tsukuda Kana , Higaki Akinori , Min Li-Juan , Mogi Masaki , Horiuchi Masatsugu
Published: July 2021

Objectives:
We reported that drinking
Citrus iyo
juice (CI) inhibited more effectively vascular remodeling in inflammation-induced vascular injury mouse model than
Citrus unshiu
juice (CU) (PLoS One. 2015). We aim to explore the possibility that citrus fruits juice drinking could attenuate cognitive decline in transient cerebral ischemia model, focusing on the effects of flavanone, hesperidin, which is more abundantly contained in CI compared with CU and has antioxidant activity.

Methods:
C57BL/6 mice were administrated 10% CI or CU in drinking water or 100 mg/kg/day hesperidin orally by gavage. Two weeks after administration, brain ischemia was induced by bilateral common carotid artery occlusion (BCCAO) for 18 minutes. Cognitive function was determined by Y-maze task 2 weeks after BCCAO (the number of alternations/total arm entry). Cerebral blood flow (CBF) was measured by a laser speckle flowmetry. Cerebral superoxide anion production 24 hours after BCCAO was measured by dihydroethidium staining and depicted as arbitrary unit of intensity vs control. mRNA levels were measured by quantitative real-time RT-PCR.

Results:
Cognitive function was impaired with the increase in superoxide anion production after BCCAO (71% (16 of 23) vs 55% (14 of 27) in Y maze). The cognitive impairment was more effectively attenuated by the administration of CI with the significant increase in CBF than CU (CI, 66% (13 of 23); CU, 61% (17 of 27)). Interestingly, we observed that the treatment with hesperidin significantly prevented cognitive decline (67% (13 of 21)) after BCCAO with the increase in CBF. Administration of CI, CU or hesperidin did not influence systolic blood pressure, body and brain weight. Superoxide anion production was attenuated by CI or hesperidin, not by CU (BCCAO, 4.0; CI, 1.2; hesperidin, 1.1; CU, 3.0). The increases in mRNA levels of NADPH oxidase subunit such as p22 and p47, and TNFα in the cortex of the brain after BCCAO seemed to be prevented by hesperidin. AT1, AT2, and Mas receptor mRNA levels in the brain cortex did not differ among these groups.

Conclusion:
Taken together, these results suggest that the intake of hesperidin in CI should prevent cognitive decline after brain ischemia at least in part due to reduction of oxidative stress and an increase in CBF.