bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 009: A Genetic Variant Of Regulatory Associated Protein Of Mtor Complex 1 (raptor) Is Associated With Blood Pressure
Authors: Aljaibeji Hayat , heydarpour Mahyar , Stanton Ana Maria , Pojoga Luminita , Williams Gordon H
Published: September 2022

Background:
The regulatory associated protein of mTOR complex I (Raptor) is essential for the activity of the mTOR1 complex. Clinical and experimental evidence shows that the pharmacological inhibition of the mTOR complex reduces blood pressure (BP) and aldosterone (ALDO) levels. We have demonstrated in wild-type male mice that Raptor expression is regulated by ALDO and salt intake. The heterozygous raptor knockdown mice exhibited BP and ALDO changes based on age and sex.

Hypothesis:
Raptor genetic variants in humans are associated with sodium (Na
+
) intake and BP.

Methods:
Study samples were obtained from the International Hypertensive Pathotype (HyperPATH) cohort. All 792 participants ( 449 male & 343 females) are of European descent with ages between (18-65) years old. Participants completed a cross-over intervention of liberal (LIB) and restricted (RES) Na
+
diets for 7 days each. Raptor genotyping by Multi-Ethnic Genotyping Array using Illumina platform yielded 135 single nucleotide variants (SNV) and assessed their association with systolic BP (SBP) with salt intake using JMP software. SNV rs99001846 was selected for further analysis using multivariate linear regression analyses as shown in the table.

Conclusion:
Carriers of the risk versus non-risk allele were associated with considerable increases in BP measurements but not with salt-sensitive BP (SSBP) and ALDO levels. To our knowledge, and despite the well-studied Raptor/mTOR pathways, no previous work has shown associations with BP in humans.
Abstract 013: Microbial Metabolites Induce Pro-inflammatory Mechanisms In Children With Chronic Kidney Disease
Authors: Bartolomaeus Hendrik , Holle Johannes , Loeber Ulrike , Behrens Felix , Bartolomaeus Theda , Anandakumar Harithaa , Wimmer Moritz I , Vu Dai Long , Geisberger Sabrina Y , Eckardt Kai-Uwe , Forslund Sofia Kirke , Thürmer Andrea , McParland Victoria , Kirwan Jennifer A , Müller Dominik , Wilck Nicola
Published: September 2022

Introduction:
Chronic inflammation is a major risk factor for cardiovascular disease in chronic kidney disease (CKD). The underlying mechanisms are incompletely understood, but may be linked to gut dysbiosis. We aim to describe the microbiota-immune interaction in a cohort of pediatric CKD, thus independent of confounding comorbidities frequently seen in adult patients.

Methods:
We analyzed the fecal microbiome, plasma metabolites and peripheral immune phenotypes in 48 children (normal kidney function (HC, n=10), CKD stage G3-G4 (CKD, n=12), G5 treated by hemodialysis (HD, n=11) or kidney transplantation (KT, n=15)) with a mean age of 10.6 ± 3.8 (mean±SD) years.

Results:
Children exhibit stage-dependently increased cardiovascular risk as seen by the presence of arterial hypertension despite anti-hypertensive medication. Serum TNF-α (2.87±1.10 (HC); 7.54±2.29 (CKD); 9.63±2.73 (HD); 5.70 ± 1.66 (KT) pg/mL) and sCD14 (1.83±0.28 (HC); 2.88±0.47 (CKD); 2.83±0.69 (HD); 2.22±0.34 (KT) μg/mL) were elevated, indicating inflammation, gut barrier dysfunction and endotoxemia. We observed compositional and functional alterations of the microbiome, including a diminished production of short-chain fatty acids (e.g. propionate 10.43±5.49 (HC); 8.95±4.66 (CKD); 2.75±3.84 (HD); 12.49±4.89 (KT) μM). Plasma metabolite analysis revealed a stage-dependent increase of tryptophan metabolites of bacterial origin (e.g. indoxylsulfate). Serum from HD patients activated the aryl hydrocarbon receptor and stimulated TNF production in monocytes (fold change over HC: 1.80±0.61), corresponding to a pro-inflammatory shift from classical to non-classical and intermediate monocytes. Moreover, unsupervised analysis (FlowSOM) of T cells revealed a loss of mucosa-associated invariant T (MAIT) cells and regulatory T cell subtypes (e.g. CCR6+ and CXCR3+ subsets) in HD patients.

Conclusions:
In conclusion, gut barrier dysfunction and microbial metabolite imbalance mediate the pro-inflammatory immune phenotype in CKD. These dysbiosis-driven immunological changes are already detectable in children with CKD, in whom comorbidities usually found in adults are absent, highlights the specificity of CKD-related microbiota-immune interaction.
Abstract 022: Impaired Parasympathetic Cardiac Modulation In Long-COVID Postural Tachycardia Syndrome
Authors: Rigo Stefano , Urechie Vasile , Diedrich Andre , Okamoto Luis E , Biaggioni Italo , Shibao Cyndya A
Published: September 2022

About 1 out of 10 patients infected with Sars-CoV2 have persistent symptoms beyond 4 weeks and some of them meet diagnostic criteria for postural tachycardia syndrome (Long-COVID POTS). The pathophysiology of Long-COVID POTS is unknown, but autonomic dysfunction may play a role. We hypothesize Long-COVID POTS patients have impaired cardiovascular autonomic reflexes and cardiac sympathovagal balance. We conducted a case-control study with patients recruited from the Vanderbilt Autonomic Dysfunction Center and an historical population of healthy controls. Hemodynamic parameters were measured before and during 75° head up tilt. Supine ECG and finger blood pressure were continuously measured for spontaneous heart rate variability analysis. The Low Frequency (0.04-0.15Hz, LF
RR
) and High Frequency (0.15-0.4 Hz, HF
RR
) oscillatory modulations of sino-atrial node discharge were computed. We included 14 Long-COVID POTS patients and 15 controls matched by age (34
±
11 vs 28
±
7; p=0.09) and BMI (26.1
±
5.3 vs 23.0
±
2.6; p=0.06). As expected, the orthostatic HR increase was higher in Long-COVID POTS compared to controls (40
±
18 vs 21
±
1, p<0.05). Spectral analysis of heart rate variability in 9 patients and 15 controls (Figure) showed that Long-COVID POTS had reduced HF
RR
(363
±
420 vs 933
±
1000 ms
2
; p<0.05) and similar LF
RR
(798
±
596 vs 962
±
1075 ms
2
; p=0.68), resulting in a greater LF/HF ratio (3.7
±
2.9 vs 1.4
±
1.3; p<0.05). Patients with Long-COVID POTS have reduced markers of cardiovagal modulation, but normal cardiac sympathetic activation. Our results suggest that parasympathetic dysfunction contributes to the pathophysiology of Long-COVID POTS.
Abstract 023: Quantification Of White Matter Lesion Volume From Clinical T1 Weighted Magnetic Resonance Images To Predict Functional Outcomes Post-thrombectomy
Authors: Kawas Mohammad Iyas , Shamulzai Ahmad , Kittel Carol , Curry Brian , Kim Jeongchul , Fargen Kyle , Whitlow Christopher , Quintero Wolfe Stacey
Published: September 2022

Background:
Endovascular treatment (EVT) has immense benefits for patients with large vessel occlusion (LVO). However, many patients do not achieve functional independence despite successful EVT. This may be due to concurrent cerebral small vessel disease (CSVD) mitigating recovery. CSVD manifests as white matter hypointensities on T1-weighted (T1w) MRI and is usually qualitatively assessed from clinical-quality MRI, which does not allow for objective quantification.

Objectives:
Implement a processing pipeline to quantify white matter hypointensity volume (WMHV) from clinical images and examine WMHV's influence on functional outcomes post successful EVT.

Methods:
We performed a retrospective analysis of the Atrium Wake Forest Stroke Thrombectomy and Aneurysm Registry (n=602) collected between 2015 - 2021. We selected patients with LVO who underwent successful EVT, defined as a Thrombolysis in Cerebral Infarction score of 2B or better. Clinical T1w images were transformed into high-resolution images using the convolutional neural network SynthSR. Then, FreeSurfer was used to quantify baseline WMHV from the side of the brain contralateral to the stroke to minimize stroke interference. To correct for head size, WMHV was adjusted to the estimated total intracranial volume and then log-transformed to address skewness.

Results:
The analysis included 213 patients (mean age 67.5 ± 14.6, 49.3% (105 of 213) female) who had MRI of sufficient quality for assessment and 90-day mRS. Baseline WMHV was significantly predictive of 90-day mRS in an ordinal regression model adjusted for baseline mRS (p<0.001). After adjusting for confounders and comorbidities, WMHV remained an independent predictor of 90-day mRS (p<0.001).

Conclusions:
Increased volume of white matter hypointensities correlates with poorer functional outcomes after mechanical thrombectomy and may attenuate EVT benefit. Furthermore, advances in neural networks enable the quantification of cerebral small vessel disease from clinical T1w MRI. Such approaches expand the utility of clinical imaging for research purposes.
Abstract 032: Afferent Renal Denervation And IL-1 Receptor Blockade Attenuate The Pathogenesis Of Hypertension In DOCA-salt Mice Similarly: Evidence For A Common Mechanism?
Authors: Baumann Daniel C , Van Helden Dusty A , Evans Louise C , Osborn John W
Published: September 2022

Emerging evidence suggests an interaction between renal inflammation and afferent renal nerves in some preclinical models of hypertension. In this study we tested the hypothesis that the inflammatory cytokine IL-1β interacts with afferent renal nerves in the pathogenesis of the DOCA-salt mouse model of hypertension. Specifically, we compared the effect of total renal denervation (TRDN) and afferent RDN (ARDN) on the development of DOCA-salt hypertension to that observed in animals receiving the IL-1 receptor antagonist anakinra.
In the first study
, 10-week-old male C57BL6/J mice were implanted with radiotelemeters for measurement of mean arterial pressure (MAP). DOCA was administered via subcutaneous pellet containing 50 mg of DOCA, controls received a drug free pellet. Uni-nephrectomy, pellet insertion, salt treatment, TRDN, ARDN, or sham denervation were all performed on the same day. TRDN and ARDN was performed through peri-axonal application of phenol and capsaicin respectively.
In the second study
, the IL-1 receptor antagonist anakinra (75mg/kg) or vehicle control (0.9% saline) was delivered via intraperitoneal injection daily 10 days post-induction of hypertension. Renal cytokine protein was quantified by Multiplex ELISA. All values reported are mean
+
SEM, all groups n=5.
In the first study
, MAP increased in sham treated DOCA-salt mice +43 ± 1 mmHg from baseline by the end of the 3
rd
week of DOCA-salt. This response was attenuated by 40% in TRDN (+26 ± 4 mmHg) and by 44% in ARDN DOCA-salt mice (+24 ± 3 mmHg). IL-1β was increased in DOCA-salt kidneys (2.1 ± 0.4 pg/mg) compared to control kidneys (0.36 ± 0.1 pg/mg).
In the second study
, anakinra similarly attenuated the increase in MAP by 45% (+21 ± 2 mmHg) compared to vehicle controls (+38 ± 1 mmHg). Neither ARDN nor IL-1 receptor antagonism had any effect on renal inflammatory cytokines IL-1β, IL-6, or TNFα. The comparable attenuation in the MAP response to DOCA-salt ARDN and anakinra treated groups as well as the unchanged inflammatory phenotype is consistent with a common mechanism of action. We hypothesize that intrarenal IL-1β activates sympathoexcitatory renal afferent nerves to increase MAP in DOCA-salt mice. Future studies are needed to directly test this hypothesis.
Abstract 039: Hybrid Intrinsic Frequency Machine Learning Approach For Calculation Of Total Arterial Compliance And Aortic Characteristic Impedance From A Single Carotid Waveform In Heart Failure With Preserved Ejection Fraction
Authors: Niroumandijahromi Soha , Vaidya Ajay , Pahlevan Niema M
Published: September 2022

Introduction:
Previous studies demonstrated that heat failure with preserved ejection fraction (HFpEF) is characterized by abnormal arterial function and left ventricle (LV)-arterial coupling. Aortic characteristic impedance (Zc) and total arterial compliance (TAC) are well-established biomarkers for quantification of the arterial function. However, the routine clinical use of these biomarkers requires both pressure and flow measurements. Intrinsic Frequency (IF) method is a novel system-based mathematical approach for the analysis of the cardiovascular dynamics that can predict HF events (Cooper et al. Hypertension, 2021 PMID: 33390053). We hypothesized that a hybrid IF-machine learning (ML) approach can compute TAC and Zc from a noninvasive carotid waveform.

Method:
We used data from the Framingham Heart Study (FHS) (n=6168). The reference values of Zc and TAC were computed from carotid pressure and aortic flow waveforms. IF parameters of carotid pressure waveform were used in a fully connected feed-forward neural network model. The model was trained/validated/tested on 80% of randomly selected data from all FHS data. The final model was tested on the remaining 20% of the data blinded to all stages of ML development.

Result:
In blind test set data, our IF-ML models showed correlations of r=0.89 and r=0.79 with the reference value of TAC and Zc, respectively (Fig 1). More importantly, the TAC and Zc from our IF-ML models showed strong correlations among HFpEF patients (r=0.9 and r=0.77 respectively) (Fig.1)

Conclusion:
Since IFs can be measured noninvasively (e.g. an iPhone), this method can be used to facilitate routine and noninvasive evaluation of TAC and Zc in HFpEF.
Abstract 047: PPARg Deacetylation Mitigates Aortic Stiffness And Aortic Perivascular Adipose Tissue (aPVAT) Remodeling In Obese Male Mice
Authors: Maddie Nicole , Carrillo-Sepulveda Maria Alicia , Qiang Li
Published: September 2022

Clinical findings show that stiffening of large arteries can precede hypertension in obesity. The causality between arterial stiffness and blood pressure is complex and the underlying mechanism remains unclear. Thoracic aPVAT, a brown-like adipose tissue (AT), undergoes phenotypic changes in obesity resulting in the loss of its protective vascular effect. Our recent findings demonstrated that peroxisome proliferator-activated receptor gamma (PPARγ) deacetylation, a post-translational modification, enhances endothelium-dependent vasodilation. Based on this evidence and PPARγ’s role in regulating AT,
we hypothesize that PPARγ deacetylation alleviates aortic stiffness and aPVAT remodeling in obesity
. Male eight-week-old C57Bl/6 mice and genetically engineered deacetylation-mimetic mice with a double lysine to arginine mutation (K268R, K293R; 2KR mice) were randomized into two groups:

Control groups

of C57Bl/6 (n=8) and 2KR mice (n=5) received a regular chow diet (5% fat, 48.7% carbohydrates [3.2% sucrose]) and

WD groups

of C57Bl/6 (n=11) and 2KR mice (n=9) received a western diet (40% fat, 43% carbohydrates [34% sucrose]) for 20 weeks. Obesity was confirmed by markedly increased body weight in the C57Bl/6 (40.47 ± 1.71 g vs. 29.89 ± 0.76 g controls, p<0.05) and 2KR mice (34.48 ± 1.68 g vs. 24.76 ± 0.59 g controls, p<0.05) at 16 weeks on WD. Pulse wave velocity data, the gold standard measurement for arterial stiffness, revealed increased aortic stiffness in the 16 weeks (5.70 ± 0.61 m/s vs. 3.82 ± 0.24 m/s controls) and 20 weeks (4.89 ± 0.21 m/s vs. 4.02 ± 0.17 m/s controls) on WD in the C57Bl/6 group. Strikingly, WD 2KR mice did not show aortic stiffness after 16 weeks (4.36 ± 0.37 m/s vs. 4.34 ± 0.54 m/s controls, p=0.75) or 20 weeks (5.00 ± 0.65 m/s vs. 5.84 ± 0.96 m/s controls, p=0.49) of WD. aPVAT from WD C57Bl/6 group exhibited profound phenotypic changes, switching from brown- to white-like AT with larger Oil Red O stained lipid droplets, while aPVAT from WD 2KR showed reduced phenotypic modifications. Whether aPVAT contributes to aortic stiffness in obesity remains poorly understood and warrants further investigation. In conclusion, our results support a protective role of PPARγ deacetylation in obesity-related vascular complications.
Abstract 054: Altered Valsalva Maneuver Hemodynamics In Postural Tachycardia Syndrome
Authors: Rigo Stefano , Urechie Vasile , Okamoto Luis E , Biaggioni Italo , Shibao Cyndya A , Wahba Amr , Elkholey Khaled , Giesecke Morgane , Muldowney James , Diedrich Andre
Published: September 2022

Postural Tachycardia Syndrome (POTS) is often associated to subtle cardiovascular autonomic alterations. Valsalva maneuver (VM) is commonly used in clinical settings to assess autonomic functions. Specific hemodynamic responses during VM phases can support POTS diagnosis and can provide pathophysiological characterization.We hypothesize that POTS patients present differences in VM morphology with respect to healthy controls. We conducted a case-control study enrolling subjects with prior clinical diagnosis of POTS and controls. ECG and finger blood pressure were continuously recorded during an against-resistance expiratory effort, producing a 30-mmHg straining pressure for 15 seconds in supine. Hemodynamic parameters were computed in absolute terms at baseline, early (VM2e) and late (VM2l) phase 2, phase 3 (VM3) and phase 4 (VM4) and in inter-phase changes. We studied 13 POTS and 12 controls matched for age (28
±2
vs 31
±3
; p=0.98) and BMI (24.2
±
1.0 vs 23.2
±
0.8; p=0.46). Mean HR was increased at baseline (80
±4
vs 69
±3
bpm; p<0.05). POTS had higher absolute SBP during VM3 (90
±4
vs 76
±4
mmHg; p<0.05) and VM4 (124
±5
vs 112
±3
mmHg; p<0.05). Figure shows higher HR increment (22
±
2 vs 12
±4
bpm; p<0.05) during VM2e and greater SBP rise (17
±
4 vs 10
±3
mmHg; p<0.05) in VM2l compared to controls. VM4 SBP overshoot increase was similar (17
±
3 vs 14
±
3 mmHg; p=0.36). POTS have higher SBP rise during VM2l and higher VM2e HR increase. These results suggest that VM analysis can aid clinical diagnosis and that maximal baroreceptor unloading creates higher tachycardic response and vasoconstriction in POTS.
Abstract 071: Hypertension Rewrites The Kidney Transcriptome And Drives Nephropathy
Authors: Grimm Rick , Tatomir Anamaria , Jung Hyun Jun , Delpire Eric , Welling Paul
Published: September 2022

Hypertensive nephropathy is a commonly diagnosed form of chronic kidney disease (CKD), but the biological processes underlying disease initiation are poorly understood. Here, we explore if non-malignant hypertension (HTN) is sufficient to initiate kidney damage and seek to identify pathways that drive disease development. We created a genetically defined hypertensive mouse by introducing activating mutations in the Ste20p-related proline alanine-rich kinase (SPAK) that are solely expressed in distal convoluted tubule cells. These constitutively active SPAK mice (CA-SPAK) develop salt-sensitive HTN due to hyperactivation of the thiazide-sensitive sodium chloride cotransporter (NCC). For these studies, CA-SPAK and control mice were fed either control salt (0.74% NaCl, CSD) or high salt diets (2% NaCl, HSD) for 24 weeks, and renal function and blood pressure were evaluated. RNASeq was performed to assess changes in the kidney transcriptional profile, the results of which were used for pathway enrichment analysis. CA-SPAK mice fed CSD develop HTN and show declining renal function starting at 26 weeks old and progresses over the next 10 weeks until they develop azotemia (BUN 30.8 vs 21.5 mg/dl; PCr - 0.42 vs 0.25 mg/dl, n=8) and albuminuria (5.2 vs 1.8 mg/day; n=8). HSD exacerbates HTN in CA-SPAK and initiates the same decline of renal function after only 8 weeks (20 weeks old). To identify changes in renal gene expression associated with the onset of function decline, we performed RNASeq on cortical tissue from both genotypes fed HSD for 8 weeks. We identified 3568 deferentially expressed genes in CA-SPAK. Pathway enrichment analysis found 3 biological processes associated with the early decline in CA-SPAK renal function that includes alterations of the filtration barrier (e.g. decreased nephrin, podocalyxin, synaptopodin, CD2AP, collagen 4a3, laminin B2), albuminuria associated genes (e.g. decreased cubilin, megalin, mucin 1), and immune system activation (e.g. increased MHC class II, T and B lymphocytes markers). Our findings from CA-SPAK mice demonstrate that non-malignant HTN can induce altered renal gene expression, the consequence of which is sufficient to disrupt kidney function resulting in the onset of hypertensive nephropathy.
Abstract 075: The Kidney-OVLT Neuroaxis Mediates Neurogenic Hypertension And Polydipsia In 2-Kidney, 1-Clip Rats
Authors: Ruiz Lauar Mariana , Pestana-Oliveira Nayara , Vulchanova Lucy , Van Helden Dusty , Collister John P , Banek Christopher T , Evans Louise C , Menani José V , Osborn John W
Published: September 2022

Renal afferent nerves mediate activation of the sympathetic nervous system and hypertension in rats with unilateral renal artery stenosis (2K1C-HTN). However, the central neural structures that mediate this response are unclear. The organum vasculosum of the lamina terminalis (OVLT), has also been implicated in the regulation of mean arterial pressure (MAP) and sympathetic activity in preclinical models of hypertension. We tested the hypothesis that afferent renal nerves and the OVLT share a common neural pathway required for the development of 2K1C-HTN. Two experiments were conducted.
1:
Male rats (n=5-9) were implanted with telemeters to measure MAP. 1-week later they received a clip on the left renal artery and were subjected to afferent renal denervation (ARDN) by periaxonal capsaicin (2K1C-ARDN) or sham (2K1C-sham) treatment of the clipped kidney.
2:
Male rats (n=6-8) were subjected to lesioning of the OVLT (OVLTx) or sham operation. 1-week later telemeters were implanted and 7 days later the left renal artery was stenosed by application of a silver clip. In both experiments, MAP was measured continuously for 6 weeks, and water intake (WI) was measured once a week. Neurogenic pressor activity (NPA) was assessed by measuring the peak MAP response to ganglionic blockade.
EXPT 1 Results:
At the end of the protocol, MAP was 165±5 mmHg in 2K1C-sham compared to 131±10mmHg in 2K-1C-ARDN rats (p<0.001). WI increased in 2K1C-sham rats peaking at 110±13 ml/day at week 2. In contrast, WI was markedly reduced in 2K1C-ARDN rats at this same time point (41±3 ml/day). NPA was increased in 2K1C-sham (-50 ± 4 mmHg) but was reduced in 2K1C-ARDN (-25 ± 3 mmHg) rats (p<0.05).
EXPT 2 Results:
At end of the protocol MAP was 162±6 mmHg in sham-2K1C rats compared to 135±8 mmHg in OVLTx-2K1C rats (p<0.001). WI peaked at 74±9 ml/day in sham lesion-2K1C compared to 52±9 ml/day in OVLTx-2K1C rats at week 2 (p<0.05). NPA was increased in sham-2K1C rats (-51 ± 3 mmHg) but was reduced in OVLTx-2K1C rats (-31 ± 4 mmHg) (p<0.05). Since both ARDN and OVLTx attenuated MAP, WI, and NPA similarly in 2K1C rats, we hypothesize that afferent renal nerves and the OVLT are linked in a common neural pathway required for the development of hypertension following renal artery stenosis.
Abstract 087: Analysis Of Blood Pressure Readings Among The Unsheltered Population Of Miami-Dade County
Authors: Seshadri Suhas R , Morgan Orly , Rasul Taha F , Bergholz Dan , Henderson Armen
Published: September 2022

Introduction:
Hypertension (HTN) can lead to adverse cardiovascular sequelae without appropriate management. People experiencing homelessness (PEH) are at increased risk of diseases yet have poor access to HTN monitoring. In particular little is known about prevalence of HTN among unsheltered PEH. Our objective is to assess baseline HTN characteristics in the unsheltered PEH population of Miami-Dade County.

Methods:
Blood Pressure (BP) measurements were obtained by in-person clinic “street runs” where medical providers meet with unsheltered PEH. Vitals were recorded in RedCap electronic medical record system. Center for Disease Control National Health and Nutrition Examination Survey (NHANES) 2017 – 2020 Pre-pandemic data set represented the general population. Descriptive statistics and independent sample t-test comparisons were performed using SPSS v26.

Results:
BP was reported in 145 interactions – participant mean age 56.2 years (SD 10.5), 79.8% Male. The total average systolic BP (SBP) 140.14 (SD 22.28), diastolic BP (DBP) 87.99 (SD 12.74). Average visit 1 (N = 94) SBP 141.10 (SD 22.82), DBP 88.46 (SD 13.24). Average visit 2 (N= 22) SBP 145.45 (SD 21.69), DBP 89.82 (SD 12.45). No significant difference was found between visits 1 and 2. Elevated BP at two visits established formal HTN diagnosis, as defined by American College of Cardiology criteria. NHANES average SBP 119.81 (SD 19.38), DBP 71.61 (SD 12.02). NHANES data compared to average Visit 1 BP showed PEH to have significantly higher SBP (p<0.0001), DBP (p<0.0001). Age and gender stratification furthered internal validation. The average BP measurements of unsheltered PEH at clinic was in American Heart Association’s HTN Stage 2 category.

Conclusion:
BP of the PEH surveyed were higher than in the general population and within pathological staging criteria for HTN. Steady results from multiple visits suggest compounding factors beyond access to care: polysubstance use disorder, smoking, poor and unbalanced nutrition, chronic stress of being unsheltered. Future studies comparing unsheltered vs sheltered PEH could elucidate more information on risks and management of this deadly and preventable disease.
Abstract 094:
Bmal1
Is Necessary For Food-Based Entrainment Of Blood Pressure And Temperature Rhythms In The Rat
Authors: Rhoads Megan K , Pollock David M
Published: September 2022

Blood pressure (BP) follows a circadian rhythm, changing throughout the day. This change is crucial for cardiovascular health and in patient populations, as loss of these rhythms are associated with increased mortality and morbidity. Though BP rhythms have been recognized as important, the factors that control and entrain them are not well-described. Since the molecular clock is ubiquitously expressed in all cells and required for many circadian processes, we tested the hypothesis that the molecular clock contributes to the timing of BP rhythms in rats. Male and female rats with whole body loss of brain and muscle ARNTL-like protein (
Bmal1
) and wild type (WT) controls (Sprague-Dawley background) were instrumented with telemeters in the abdominal aorta and placed in 12:12h light dark cycle (LD) to measure BP and core body temperature (TMP). Next, animals were placed in constant darkness (DD) for four weeks and then placed on a 12-hour time restricted feeding regimen (DD-TRF) for five days. Cosinor analysis was used to analyze BP and TMP rhythms. In a standard LD cycle, systolic BP (SBP) and TMP rhythms of both
Bmal1
-knockout (
Bmal1-
KO) and WT rats have similar amplitudes (2-way ANOVA for SBP and TMP, both p>0.05) which peak around zeitgeber time (ZT)18. During DD, WTs have SBP and TMP rhythms peak at circadian time (CT)19, while
Bmal1
-KO rats have SBP and TMP rhythms that peak at CT 12. SBP amplitude is lower in all groups during DD compared to LD (WT males: 6.0±0.7 vs 3.8±0.7 mmHg; WT females: 7.2±0.9 vs 5.6±0.3 mmHg; KO males: 5.4±0.6 vs 4.7±0.4 mmHg; KO females: 6.2±0.6 vs 5.3±0.8 mmHg; 3-way ANOVA, p<0.05 for light cycle). During DD-TRF (CT 14.5 – 2.5), SBP and TMP rhythms of WTs peak at CT22.
Bmal1
-KO rats have SBP and TMP rhythms that peak during CT16. SBP amplitude is lowered in
Bmal1
-KO rats during DD-TRF compared to DD (KO males: 2.0±0.7 mmHg; KO females: 3.8±0.6 mmHg) but not in WT rats (WT males: 3.8±0.3 mmHg; WT females: 5.1±0.4 mmHg; 3-way ANOVA, p<0.05 for feeding time, sex, and feeding time*genotype). These data suggest that the molecular clock component
Bmal1
is necessary for food-based entrainment of SBP and temperature rhythms in the absence of a regular light cue. Food, light cycle, and the molecular clock may all contribute to the timing and amplitude of SBP and TMP rhythms.
Abstract 096: Adrenal-specific KO Of The Circadian Clock Protein Bmal1 Alters Blood Pressure Rhythm
Authors: Costello Hannah M , Crislip Gene R , Cheng KitYan , Matheny Irma J , Mckee Annalisse , Juffre Alexandria , Bratanatawira Phillip , Mendez Victor M , Wingo Charles , Douma Lauren , Gumz Michelle L
Published: September 2022

BMAL1 is a core circadian clock protein that regulates most physiological functions, including blood pressure (BP). Global BMAL1 knockout (KO) male mice exhibit reduced, non-dipping BP and loss of diurnal rhythm of renal sodium (Na) excretion. Although, BP and renal Na excretion rhythm remained intact in kidney-specific BMAL1 KO male mice. The adrenal gland synthesizes hormones which influence BP rhythm and renal electrolyte handling. The role of adrenal BMAL1 in the regulation of BP and renal function remains unknown. The goal was to test the hypothesis that adrenal BMAL1 is required for normal circadian rhythms of BP and renal Na excretion.

Adrenal-specific aldosterone synthase Cre positive (AS)-BMAL1 KO male mice (
n
=5) and littermate Cre negative, floxed control (CNTL) male mice (
n
=6) underwent a telemetry study to measure BP. Cosinor analysis was performed to assess BP rhythms. During telemetry recordings, mice were placed in metabolic cages for 5 days on a normal salt diet. The latter 3 days, 12 h urine samples were collected before each light-dark Zeitgeber (6AM and 6PM/ Zeitgeber Time (ZT)0 and ZT12) to measure night/day patterns in renal Na excretion. Kidneys were collected from a separate cohort of mice (
n
=7-8/genotype) at ZT0 and ZT12 for gene expression analysis of key Na transporters.

No BMAL1-dependent changes in the 24 h averages for BP were observed. Cosinor analysis revealed significant differences in BP rhythm, however. The period (time taken for a full circadian cycle, ~24 h) was significantly shortened for BP in AS-BMAL1 KO mice vs. CNTL (23 h 31 vs 24 h 16,
p
=0.01). Acrophase (the time at which BP peaks) was shifted ~2 hours later in KO mice (KO ZT17 h 38 vs CNTL ZT15 h 45,
p
=0.002). The MESOR (midline estimating statistic of rhythm) of BP remained similar between groups (KO 133.5 mmHg vs CNTL 132.7 mmHg,
p
=0.904). Day/night Na excretion was not different in AS-BMAL1 KO mice vs. CNTL (ANOVA interaction
p
=0.168). This was consistent with a lack of genotype effects on gene expression for NCC, α, β, or γ ENaC. Significant time of day effects were observed for all 4 genes (all with
p
<0.001).

In conclusion, BMAL1 KO in the adrenal gland altered BP rhythm, with no changes in renal Na excretion. This work is the first to investigate the role of adrenal BMAL1 on BP regulation.
Abstract 111: Proposing A New ‘Gateway Food Model’ For Adolescent Eating Behavior And Its Implications For Modifiable Hypertension Risk Factors
Authors: Balhara Maria
Published: September 2022

Background:
During COVID-19, this study examined data on adolescents' eating habits. It proposes a new 'gateway food model' for ultra-processed foods (UPF). This model shows that certain UPFs when increased (decreased) drive consumption of other UPFs as well. This has important implications for managing hypertension risk factors since studies show that those in the highest tertile of UPF consumption have a higher risk of hypertension (adjusted HR, 1.21; CI, 1.06, 1.37; p = 0.004) (Mendonca, 2016).

Methods:
The study enrolled 315 participants aged 13-19 years in Florida, U.S. Participants' PIE scores (Processed Intake Evaluation scores, scale 0-100), were calculated based on averaged consumption of 12 ultra-processed food products. PIE scores, before COVID-19 in 2019, and after COVID-19 restrictions were eased in 2022, were assessed in the study.

Results:
The participants’ mean age was 16.2±1.4 years. The study classified participants into UPF+ (n=135) and UPF- (n=180) groups according to whether they increased or decreased their UPF intake during COVID-19. For both groups, a stepwise regression was employed to identify significant factors for change in UPF intake. In the UPF+ group, increased intake of candy, store pastries, or frozen desserts was associated with increased UPF intake across all other UPFs as well (+31.2, +12.0, or +10.5 respective change in PIE score, p<0.01). Correspondingly, in the UPF- group, reduced intake of biscuits, white bread, or processed meat was associated with decreased overall UPF intake across all other UPFs as well (-9.6, -9.4, -8.6 respective change in PIE score, p<0.01).

Conclusions:
Hypertension can begin during childhood and may be mediated by a focus on modifiable risk factors such as high UPF intake. These results indicate that for adolescents whose consumption of UPFs has not yet been established, certain gateway UPFs (candy, store pastries, and frozen desserts) should be given priority for preventive dietary interventions since increased intake in these UPFs leads to consumption of all other UPFs as well. In contrast, if an adolescent's UPF eating is already established, other UPFs (biscuits, white bread, or processed meat) can be targeted by dietary interventions as they decrease intake across all other UPFs.
Abstract 112: Role Of Endogenous Brain Melanocortin-4 Receptor Activation In Regulating Blood Pressure And Metabolic Function In Offspring Of Parents With Obesity
Authors: da Silva Alexandre A , Moak Sydney , Dai Xuemei , Borges Gisele , Omoto Ana C , Gulke Rodrigo , Wang Zhen , Li Xuan , Mouton Alan J , Hall John E , do Carmo Jussara M
Published: September 2022

We previously demonstrated that activation of the central nervous system (CNS) melanocortin system modulates sympathetic nerve activity (SNA) and blood pressure (BP) in obese Zucker rats and spontaneously hypertensive rats (SHRs). In the present study, we examined whether endogenous activation of the brain melanocortin-4 receptors (MC4R) contributes to the regulation of BP and metabolic function in adult male (24-26 weeks-old) obese and lean offspring from parents fed a normal (N) or high fat diet (H). The rats were implanted with telemetry probes to measure BP and heart rate (HR) 24-hrs/day, and an intracerebroventricular (ICV) cannula was placed into the lateral ventricle. After 1 week to recover from surgery and 2 days of control measurements, the MC4R antagonist (SHU-9119) was infused (1 nmol/h, ICV) for 7 days followed by a 7-day recovery period. MC4R antagonism markedly increased food intake in all groups; however, the increase was more pronounced in obese offspring from obese H-fed parents (HH), especially when analyzing the net cumulative increase in food intake during the 7 days of treatment (191±11 vs. 136±14, 65±18 and 72±12 g) compared with obese offspring from lean N-fed parents (NH), lean offspring from obese H-fed parents (HN) and lean offspring from lean parents (NN), respectively. This increased food intake was associated with more weight gain in HH compared with NH, HN and NN offspring (Δ: 92±12 vs. 81±17, 52±11 and 38±9 g). Plasma leptin and insulin levels were markedly increased in HH offspring compared to NH, HN and NN offspring. Compared to NH and NN offspring from lean parents, HH and HN offspring from obese parents exhibited higher baseline mean arterial pressure (125±2 and 122±3 vs. 118±1 and 113±3 mmHg) and greater reduction in BP during SHU-9119 infusion (average last 3 days of infusion: -14.3±0.1 and -5.6±0.5 vs. -9.8±0.2 and -3.4±0.2 mmHg, respectively). The reduction in HR during SHU-9119 infusion, however, was more pronounced in NH and NN groups compared with HH and HN offspring (average last 3 days of infusion: -55±2 and -43±1 vs. -34±2 and -34±1 bpm). These results suggest that endogenous activation of brain MC4R may contribute to the elevated BP in obese offspring but not lean offspring from obese parents.
Abstract 114: Metabolic Adaptation During Obesity Is Associated With G Protein Switching By The Angiotensin At1a Receptor In Agrp Neurons
Authors: Balapattabi Kirthikaa , Ritter McKenzie L , Mouradian Gary C , Hodges Matthew R , Sigmund Curt D , Grobe Justin L
Published: September 2022

Obesity represents the single greatest impediment to continued improvements in hypertension and cardiovascular disease. Prolonged obesity is associated with “Resting Metabolic Rate (RMR) adaptation” (ie, reduced RMR relative to body composition), and RMR adaptation is proposed to explain resistance to weight loss / weight maintenance after obesity is established. Previously we showed that angiotensin II (ANG)
Agtr1a
(AT1A) receptors expressed in Agouti-related peptide (AgRP) neurons of the hypothalamic arcuate nucleus (ARC) are required for integrative control of RMR. We hypothesize that changes in AT1A signaling in AgRP cells underlie the development of RMR adaptation. ARC slices from mice expressing tdTomato in AgRP cells (
Agrp
-Cre x Ai9) were used for cell-attached voltage clamp recording of AgRP neurons. ANG inhibited ~33% of AgRP neurons via an AT1A-dependent mechanism (deemed a “Type 1i” response, which was inhibitable by losartan (LOS) or genetic deletion of AT1A; Firing rate; aCSF:0.85 ± 0.03 vs ANG:0.20 ± 0.04 vs ANG+LOS:0.91 ± 0.11 Hz, p<0.05) that was also blocked by the Gαi inhibitor, pertussis toxin (PTX), but not by the Gαq inhibitor, BIM-46187 (Δ Firing rate: PTX: -0.39 ± 0.09 Hz, p<0.05 vs BIM: 0.10 ± 0.09 Hz). After 10 weeks of high-fat feeding, roughly half of Type 1 cells exhibited a spontaneous switch from the ANG/AT1A-mediated inhibitory (Type 1i) response to an ANG/AT1A-mediated stimulatory response (“Type 1s”; Firing rate; aCSF: 0.86 ± 0.03 vs ANG:1.10 ± 0.12 vs ANG+LOS:0.82 ± 0.03 Hz, p<0.05), which was blocked by BIM-46187, but not by PTX (Δ Firing rate: PTX: 0.07 ± 0.06 Hz vs BIM: 0.49 ± 0.06 Hz, p<0.05). AAV delivery of Cre-inducible DREADDs into the ARC of lean
Agtr1a
-Cre mice was then used to study the effects of Gαi vs Gαq signaling in Type 1 AgRP cells upon RMR control. Activation of the Gαi-coupled hM4Di DREADD in AT1A-expressing cells of the ARC was sufficient to increase RMR (+25% from baseline, n=8-10, p<0.05), but activation of a Gαq-coupled DREADD had no effect. We conclude (i) that the AT1A receptor is expressed by a unique subtype of AgRP neuron; (ii) that inhibitory AT1A-Gαi signaling in the Type 1 AgRP cell stimulates RMR; and (iii) that loss of AT1A-Gαi coupling in these cells is sufficient to explain obesity-associated RMR adaptation.
Abstract 127: Nox5 Expression In A Vascular Smooth Muscle Cell-specific Manner Induces Fibroblast To Myofibroblast Differentiation
Authors: Montezano Augusto C , Rios Francisco J , Blaikie Zachariel , Saad Tomador E , Camargo Livia , Beattie Wendy , Jaisser Frederic , Guzik Tomasz , Graham Delyth , Touyz Rhian M
Published: September 2022

Mice expressing human Nox5 (hNox5) in VSMC exhibit cardfiovascular fibrosis, where mechanisms are unknown. We postulated that VSMC-Nox5 promotes fibroblast to myofibroblast differentiation that contributes to fibrosis. Fibroblasts were cultured from wildtype (WT) and hNOX5 mice. Mice (20 weeks old) were infused with Ang II (600 ng/Kg/day) for 28 days and renal fibrosis/inflammation studied. Markers of myofibroblasts (αSMA), and pro-fibrotic and inflammatory signaling molecules were assessed by qPCR and immunoblotting. Inflammatory infiltrate was assessed by FACS. Fibroblasts from Nox5 mice exhibited increased mRNA of markers of myofibroblast αSMA (2
-ddC
:1.54±0.05
vs.
WT 0.78±0.17) and Myocd (2
-ddC
:1.36±0.17
vs.
WT 0.39±0.22), as well as, pro-fibrotic markers, Col1A1 (2
-ddC
:1.74±0.16
vs.
WT 0.67±0.11), Col3A1 (2
-ddC
:1.74±0.18
vs.
WT 0.96±0.24) and TIMP3 (2
-ddC
:2.65±0.25
vs.
WT 0.38±0.07), p<0.05. mRNA expression of CD36 (2
-ddC
:1.37±0.07
vs.
WT 86±0.24), TNFα (2
-ddC
:1.32±0.2
vs.
WT 0.71±0.17) and TNFR1 (2
-ddC
:1.26±0.04
vs.
WT 1.02±0.10) were increased, while CD68 expression was decreased (2
-ddC
:0.82±0.11
vs.
WT 1.36±0.18) in fibroblasts from Nox5 mice (p<0.05). In Nox5 mice fibroblasts, ROS production and TGFβ protein expression (AU:1.8±0.05
vs.
WT 1.4±0.06), as well as TGFβR2 gene expression (2
-ddC
:2.04±0.17
vs.
WT 0.57±0.12), were increased (p<0.05). mRNA of DNMT3a and TET2, DNA methylation regulatory enzymes, were also increased in fibroblasts from Nox5 mice, p<0.05. Kidneys from Ang II-infused Nox5 mice exhibited significant perivascular fibrosis and inflammatory cell infiltration compared to WT, as well as increased protein expression of TGFβ (AU: 3.59±0.8
vs.
WT 1.54±0.2) and IL-11 (AU: 0.64±0.08
vs.
WT 0.39±0.04), p<0.05; where levels of macrophage F4/80+ cells (%:24±2 vs WT 18±1, p<0.05) and levels of cytotoxic CD8+ T cells were increased, p<0.05. Kidney expression of vimentin (AU:1.01±0.05 vs WT 0.85±0.03) and αSMA (AU:0.44±0.03 vs WT 0.33±0.01), were increased in Nox5 mice (p<0.05). Nox5 regulates fibrosis by inducing fibroblast-to-myofibroblast differentiation, possibly through increased ROS. These processes may be important in Nox5-assocated cardiovascular-renal fibrosis.
Abstract 128: Loss Of
Gstm1
Augments Kidney Neutrophil Population In Angii-induced Hypertension
Authors: Chen Luojing , Beane Timothy J , Wang Yves , Cunningham Jason J , Liu Jing , Wu Jing , Le Thu H
Published: September 2022

Background:
Glutathione-S-transferase Mu1(
Gstm1
) gene, a member of Glutathione-S-transferases (GST) superfamily, encodes an enzyme that functions in the detoxification of electrophilic compounds. The common
GSTM1
deletion variant in humans is associated with increased risks of chronic kidney disease (CKD) progression and incident end stage kidney failure. We reported that deletion of
Gstm1
increases oxidative stress, kidney inflammation and injury in angiotensin II induced hypertension (Ang II-HTN) in mice. At 4 weeks of Ang II-HTN, neutrophils, CD4+T cells, and F4/80+ cells were significantly increased in
Gstm1
knockout (KO) kidney. While a link between oxidative stress and immune activation in hypertension has been well documented, the molecular mechanism by which
Gstm1
regulates immune cell activation in hypertension is unknown.

Methods:
To further characterize the inflammatory response in GSTM1 deficiency,
Gstm1
KO and wild-type (WT) male mice at ~ 12 weeks of age were subjected to Angiotensin II at 1000 ng/kg per minute for 4 days via a mini osmotic pump. The kidney cells and bone marrow cells were isolated for flow cytometry analysis.

Results:
At baseline, there were no differences in inflammatory cell populations including neutrophils between WT and
Gstm1
KO mice. At Day 4 of Ang II-HTN,
Gstm1
KO kidneys exhibited about a 2.3 fold increase in neutrophil population (CD45
+
Ly6G
+
CD11b
+
), compared to WT control mice (10 WT and 8
Gstm1
KO mice, p=0.0075). Interestingly, CD45+ bone marrow cells isolated from both
Gstm1
KO and WT mice have similar percentile of neutrophil populations ; however, neutrophils in
Gstm1
KO bone marrow express relatively higher levels of CXCR2. Unlike at 4 weeks, there was no difference in other inflammatory cells at Day 4.

Conclusion:
Deletion of
Gstm1
increases renal neutrophil population early in Ang II-HTN and CXCR2 expression in bone marrow neutrophils.
Gstm1
may play a role in regulating neutrophil migration and recruitment. Further studies are needed to delineate whether GSTM1 deficiency drives kidney injury via early neutrophil migration, which could shed light on potential therapeutic target for CKD progression in those genetically susceptible.
Abstract 130: Isolevuglandins Drive Neutrophil Migration In Hypertension And Are Essential For The Formation Of Neutrophil Extracellular Traps
Authors: Krishnan Jaya , De La Visitacion Nestor , Hennen Elizabeth , Harrison David G , Amarnath Venkataraman , Patrick David
Published: September 2022

Introduction:
Neutrophil extracellular traps (NETs) consist of decondensed chromatin and proteins including citrullinated histone 3, myeloperoxidase, and neutrophil elastase . Previous studies describe a role of neutrophils and NETs in hypertension and associated end-organ damage. Isolevuglandins (IsoLGs) are products of lipid peroxidation that play a role in immune activation in hypertension. We hypothesized that isoLGs are necessary for the process of NETosis and neutrophil migration in hypertension.

Methods:
C57BL/6
mice were treated with 490 ng/kg/min angiotensin (Ang) II and vehicle or the isoLG scavenger, 2-hydroxybenzylamine (2HOBA). Single cell sequencing was performed on spleens. NETs were quantified by flow cytometry and immunofluorescence. Human neutrophils were isolated and treated with ionomycin and vehicle or ethyl-2HOBA (Et2HOBA). Neutrophil chromatin expansion was determined by live cell confocal microscopy.

Results:
Single cell sequencing revealed increased splenic neutrophil accumulation following Ang II treatment. This was attenuated with 2HOBA co-treatment (Ang II 7.78%, Ang II + 2HOBA 2.46%, n=3). Flow cytometry revealed a marked increase in aortic NET accumulation that was reduced with 2HOBA (Sham 304 ± 110.6, Ang II 3,522 ± 928.6, Ang II + 2HOBA 1,007 ± 340.9 NETs, n=6-7). Immunofluorescence staining of kidneys revealed an increase in NET area in Ang II treated mice and a reduction with 2HOBA co-treatment (Sham 75.64 ± 27.2, Ang II 636.9 ± 105.0, Ang II + 2HOBA 14.98 ± 7.5 μm
2
, n=4-6). Ionomycin induced NETosis of isolated human neutrophils was associated with isoLG adduct accumulation that was attenuated with Et2HOBA co-treatment (54.24 ± 11.77% vs 1.78 ± 0.41%, n=5). Live cell confocal microscopy revealed NET area was increased 9.2-fold with ionomycin treatment compared to control. Pretreatment with Et2HOBA attenuated this response. Finally, isoLGs directly disrupt nucleosome assembly
in vitro
.

Conclusion:
These findings demonstrate an essential role of isoLGs in NETosis and neutrophil migration in hypertension. Moreover, they suggest a role of isoLG scavengers in the treatment of hypertension and additional NET-associated diseases including atherosclerosis and lupus.
Abstract 132: Reduction Of Bone Quality In A Murine Model Of Essential Hypertension Relative To Age
Authors: Hennen Elizabeth M , Ao Mingfang , de la Visitacion Nestor , Chen Wei , Uppuganti Sasidhar , Rendina-Ruedy Elizabeth , Nyman Jeffry , Harrison David G
Published: September 2022

Autoimmune and inflammatory diseases such as obesity and cancer are highly linked to altered bone growth and osteoporosis. Hypertension (HTN) is an inflammatory condition associated with reduced bone mineral density and increased risk for fragility fractures in adults. As cases of pediatric HTN rise in the United States, HTN may increase bone loss in children and future risk for osteoporosis. We hypothesized that HTN-induced osteoporosis in young mice reduces bone quality like that of aging. To assess this, 3.5- or 16-month-old male C57BL/6J mice received Angiotensin (Ang) II (490 ng/kg/day) or vehicle infusion by subcutaneous osmotic mini-pumps. After 6-weeks of infusion, the lumbar vertebral bodies (VB) were harvested, and analyzed by high-resolution micro-computed tomography and finite element analysis. In young mice, Ang-II induced HTN caused reductions in bone volume fraction (33.4 ± 0.8 vs 25.4 ± 1.1 %, p<0.0001) and trabecular thickness (66.4 ± 1.1 vs 54.3 ± 1.5 μm, p<0.0001). HTN reduced the estimated failure force (24.3 ± 0.7 vs 16.1 ± 1.1 N, p<0.0001) in young mice. In contrast to young mice, in aged mice Ang-II infusion did not induce bone loss; however, at baseline, the old mice exhibited reduced bone quality like that of hypertensive young mice: bone volume fraction (22.5 ± 0.7 vs 25.4 ± 1.1 %, p=0.2928), trabecular thickness (58.0 ± 1.5 vs 54.3 ± 1.1 μm, p=0.3866), and estimated failure force (17.6 ± 0.8 vs 16.1 ± 1.1 N, p=0.6517). To ascertain the impact of inflammation in the bone marrow microenvironment, the bone marrow was analyzed by flow cytometry. The number of CD4
+
T cells producing IL-17A was increased in hypertensive vs normotensive young mice (230.0 ± 8.9 vs 167.3 ± 16.6 cells per 1 million events, p=0.0035), as were dendritic cells (408.3 ± 29.1 vs. 229.1 ± 20.5 cells per 1 million events, p<0.0001). CD4
+
T cells producing IFN-γ also rose (2845 ± 129 vs 2437 ± 174 cells per 1 million events, p=0.07) in young hypertensive mice. Both normotensive and hypertensive old mice experienced overactive inflammatory responses compared to the young group. Thus, HTN mimics aspects of aging on bone health, causing inflammation in the bone marrow and osteoporosis. Efforts to detect and treat HTN in children may deter untoward events related to bone loss in adulthood.