bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 231: Hydrogen Sulfide Treatment Reduces Hyperglycemic Effects via Activation of Adenosine Monophosphate Activated Protein Kinase In Vitro
Authors: Kundu Sourav , Pushpakumar Sathnur B , Tyagi Suresh C , Sen Utpal
Published: July 2021

Hydrogen sulfide (H
2
S) is well known as a potent vasodilator and signaling molecule under normal and pathophysiological conditions. Previously, we reported that in hyperglycemia (HG), impairment of cystathionine β synthase/ cystathionine lyase (CBS/CSE) decreases H
2
S production leading to vascular remodeling. Treatment with H
2
S mitigated the adverse effects; however, its precise mechanism was unknown. Literature reports suggest that hyperglycemia suppresses adenosine monophosphate-activated protein kinase (AMP-K) pathway and increases autophagy leading to extracellular matrix (ECM) remodeling. Liver kinase B1 (LKB1) is a protein kinase which has been reported to control the activity of AMP-K. Activation of LKB1, in turn, is regulated by two pseudokinases, STE-20 related protein (STRAD) and mouse protein-25 (MO25). In this study, we hypothesized that H
2
S mediates its effects by the formation of a tri-molecular complex (STRAD/MO25/LKB1) leading to the activation of AMP-K and modulation of autophagy. Mouse glomerular endothelial cells were used in this study. Under normoglycemic (NG) and HG conditions, cells were treated without or with H
2
S and activators/inhibitors of the signaling molecules above. The expression of CBS/CSE was diminished by 3-fold under HG compared to NG. H
2
S production was also decreased [3.5 vs. 7.2 μM/L (HG vs. NG)]. HG decreased LKB1 by 5-fold and AMP-K by 14-fold compared to NG. Autophagy marker LC3A/B ratio was similarly decreased in HG. The expression of periostin, a marker of renal disease progression, was higher (Relative intensity (RI) = 1.9 ± 0.64) in HG compared to NG (RI= 1.4 ± 0.18). In HG, administration of H
2
S activated STRAD by 4-fold and MO25 by 3-fold causing concomitant phosphorylation of LKB1 (5-fold increase) eventually leading to AMP-K phosphorylation (13-fold increase). Interestingly, phosphorylated AMP-K inhibited autophagy and reduced ECM protein accumulation. Our findings suggest that the protective effect of exogenous H
2
S in hyperglycemia is mediated by AMP-K activation involving STRAD and MO25 pseudokinases.
Abstract 234: High Glucose Exacerbates the Lipopolysaccharide-induced Impairment of Nitrergic Relaxation to Electrical Field Stimulation of Rat Corpus Cavernosum
Authors: Stallmann-Jorgensen Inger S , Webb R. Clinton
Published: July 2021

Hypertension (HTN) and diabetes (DM) are comorbid conditions, each associated with inflammation. Lipopolysaccharide (LPS) is elevated in the serum of patients with DM and capable of robustly activating the immune system. Risk of erectile dysfunction (ED) is increased in both HTN and DM. Vascular relaxation is needed to regulate vascular tone and erectile function. Our previous studies showed that corpus cavernosum (CC) nitrergic relaxation to electrical field stimulation (EFS) was reduced after LPS exposure. It is not known whether LPS-induced inflammation plays a role in DM-associated ED. Our study aim was to examine vascular function of rat CC under high glucose conditions in the presence of LPS. We hypothesized that high glucose would exacerbate the LPS-induced decrease in EFS relaxation. Isolated rat CC strips incubated with control (5mM) or high glucose (HG, 25 mM) media with or without LPS (1 ug/mL) for 6 h. CC strips were mounted in a myograph and pre-contracted with phenylephrine (PE, 10
-5
M) before eliciting relaxation responses using 20-volt stimuli of 1, 2, 4, 8, and 16 Hz. Four Hz produced the half maximal response (%PE contraction) and was used to compare treatment effects. LPS-treated CC (7.13±1.53%) relaxed less than Control CC (19.1±2.67%). The decrease in relaxation was greatest in HG+LPS-treated CC (-3.58±1.43%), Fig. 1. Thus, we show that the LPS-induced reduction in relaxation is exacerbated in the HG+LPS condition, suggesting that elevated LPS and hyperglycemia act synergistically in the promotion of vascular dysfunction and ED.
Abstract 243: Chloroquine Treatment Increases the Threshold of Aortic Contractile Responses to Norepinephrine in a Nitric Oxide Synthase-dependent Manner in Spontaneously Hypertensive Rats
Authors: McCarthy Cameron G , Wenceslau Camilla F , Goulopoulou Styliani , Spitler Kathryn , Matsumoto Takayuki , Webb R. Clinton
Published: July 2021

Toll-like receptors (TLRs) are pattern recognition receptors of the innate immune system that are located either on the plasma membrane or on membrane of endosomes. TLR activation in immune cells leads to a pro-inflammatory phenotype and TLRs have been associated with the development of hypertension. However, the role of TLRs in the development of vascular dysfunction, a hallmark of hypertension, has not been extensively investigated. Chloroquine (CQ), due to its ability to inhibit autophagy and block lysosomal degradation, has been used as a non-specific inhibitor of TLRs located on endosomes. We hypothesized that treatment with CQ (40mg/kg/day) for 21 days would attenuate aortic contractile responses in young spontaneously hypertensive rats (SHRs; 5-6 weeks old) compared to saline (Veh) control. Concentration response curves to norepinephrine (NE; 10
-11
-10
-6
M), in the presence or absence of nitric oxide synthase (NOS) inhibitor L-NNA (10
-4
M), were performed in isolated aortic rings
ex vivo
on a pin myograph. CQ increases the threshold of aortic contractile responses to NE compared to Veh (logEC
20
CQ: -8.8±0.1 vs. Veh: -9.6±0.3, p<0.05). In the presence of L-NNA, there was a significant difference between CQ and CQ+L-NNA (logEC
20
CQ: -8.8±0.1 vs. CQ+L-NNA: -9.4±0.2, *p<0.05) (A); however, this difference was absent between Veh and Veh+L-NNA (logEC
20
Veh: -9.4±0.3 vs. Veh+L-NNA: -10.0±0.4, p>0.05) (B). These data illustrate that CQ improves the threshold for SHR aortic contraction to NE by preserving NO. Therefore, maintenance of NOS activity and NO bioavailability by inhibition of endosomal TLRs could be a therapeutic target against the development of hypertension.
Abstract 25: Angiotensin AT
1A
Receptors on Leptin Receptor-Expressing Cells are Required for the Blood Pressure and Metabolic Rate Effects of Leptin
Authors: Grobe Justin L , Claflin Kristin E
Published: July 2021

Circulating leptin and the local brain renin-angiotensin system (RAS) both contribute to the control of food intake (FI), resting metabolic rate (RMR) and blood pressure (BP), and both have been postulated to contribute to obesity-hypertension. Here we examined the provocative hypothesis that the brain RAS is required for (or mediates) the RMR- and BP-stimulating effects of leptin. To create animals lacking the AT
1A
receptor specifically in cells expressing the leptin receptor (“KO”), mice with a flox’ed version of the endogenous angiotensin AT
1A
receptor gene (AT
1A
flox
) were crossed with mice expressing cre-recombinase via the leptin receptor promoter (ObR-Cre). Body mass, body composition, blood chemistry, glucose tolerance, and FI behaviors were essentially unchanged through 34 weeks of age in mice maintained on standard chow (Teklad 7013). In contrast, anesthetized BP (MAP; control n=9, 91.6 ± 4.1, vs KO n=8, 78.0 ± 3.7 mmHg) and heart rate (351 ± 13, vs 308 ± 11 BPM) were reduced in KO mice (both P<0.05). Further, interscapular brown adipose (BAT SNA, 112 ± 22, vs 22 ± 35 % above baseline at 3 hr) and renal (154 ± 19, vs 53 ± 23 % above baseline at 3 hr) sympathetic nerve activity responses to acute leptin injection (60 μg, i.v.) were completely abolished (both P<0.05). When maintained on a 45% high fat diet (OpenSource
D12451
) to increase endogenous leptin production, KO mice exhibited accelerated body mass (control n=15, -0.1 ± 0.1, vs KO n=4, +1.7 ± 0.5 g/wk) and fat mass (+2.9 ± 0.5, vs +4.9 ± 1.1 g/5 wk) gains (both P<0.05), likely due to normal FI behaviors but a 18% reduction in RMR (control n=16, 0.196 ± 0.011, vs KO n=7, 0.161 ± 0.004 kcal/hr at 30°C, P<0.05). We conclude that expression of angiotensin AT
1A
receptors on leptin-sensitive cells is required for the metabolic rate and cardiovascular effects of leptin. Ongoing studies are focused on identifying the brain regions and subsets of leptin receptor-expressing cells in which this RAS-leptin cross-talk occurs, and the directionality and molecular mediators of this interaction. We hypothesize that uncontrolled or pathological activity of the brain RAS may thus help explain the clinically variable effects of leptin, and contribute to the mechanism(s) of selective leptin resistance and obesity-hypertension.
Abstract 260: Pedometer-assessed Workplace Walking Program Improves Cardio-Metabolic Profile Among the University’s Workforce
Authors: Veerabhadrappa Praveen , Bhat Sushma , Weiss Heather , Michael Chelsey
Published: July 2021

Introduction-
The cost of physical inactivity in the workplace setting is significant. The purpose of this study was to evaluate the association between pedometer-assessed physical activity with cardio-metabolic outcomes such as, body weight, blood glucose levels, lipid profile among the University’s academic faculty and staff.

Methods-
Twenty nine (9M/20F, 50±6yrs; BMI 28.4±4.2 kg/m
2
) apparently healthy participants who were sedentary, non-smoking, non-diabetic, free of cardiovascular disease, not on antihypertensive or cholesterol medications were recruited from the University workforce. Fasting blood glucose and lipid profile were analyzed using Cholestech LDX analyzer, before and after intervention. Pedometer settings were personalized and participants were instructed to maintain their regular diet during the study period. Participants completed a pedometer-based walking intervention (step-goal: 10,000-steps/day, 5-days/week, 4-weeks).

Results-
Baseline vs. post-intervention (Mean±SD) for total cholesterol (202.2±40.1 vs. 193.1±42.1 mg/dl; p≤0.05), blood glucose (101.2±8.7 vs. 97.8±8.9; g/dl; p=0.032), systolic blood pressure (BP; 120.7±11.1 vs. 115.1±11.1 mmHg; p=0.003) and diastolic BP (78.6±6.6 vs. 73.8±5.5 mmHg; p<0.0001) were statistically significant. Step-counts significantly increased from baseline to post-intervention (9057.7±3588.9 vs.10319.2±3177; p=0.021). Change in step-count (wk 1 to wk 4) were associated with changes in blood glucose (r=-0.39; p=0.048); diastolic BP (r=-0.43; p=0.029) and BMI (r=-0.45; p=0.022).

Conclusion-
Our preliminary study modestly increased workday walking by ~12% over four weeks, and significantly improved the cardio-metabolic outcomes among the University workforce. This suggests that, workplace physical activity programs could contribute to the achievement of 10,000 steps/day, which might maximize physical activity participation.
Abstract 263: Differential Effects of 17ß-Estradiol and 16a-Hydroxyestrone in Oxidative Stress and Proliferative Responses in Human Pulmonary Artery Smooth Muscle Cells - Implications in Pulmonary Arterial Hypertension
Authors: Hood Katie Y , Montezano Augusto C , MacLean Margaret R , Touyz Rhian M
Published: July 2021

Women develop pulmonary arterial hypertension (PAH) more frequently than men. This may relate, in part, to metabolism of 17β-estradiol (E2), leading to formation of the deleterious metabolite, 16α-hydroxyestrone (16α OHE1), which plays a role in the remodelling of pulmonary arteries. Molecular mechanisms whereby 16αOHE1 influences PASMC remodelling are unclear but ROS may be important, since oxidative stress has been implicated in the pathogenesis of PAH. We hypothesised that E2 and 16αOHE1 leads to Nox-induced ROS production, which promotes PASMC damage. Cultured PASMCs were stimulated with either E2 (1nM) or 16αOHE1 (1nM) in the presence/absence of EHT1864 (100μM, Rac1 inhibitor) or tempol (antioxidant; 10μM). ROS production was assessed by chemiluminescence (O2-) and Amplex Red (H2O2). Antioxidants (thioredoxin, peroxiredoxin 1 and NQ01), regulators of Nrf2 (BACH1, Nrf2) and, marker of cell growth (PCNA) were determined by immunoblotting. E2 increased O2- production at 4h (219 ± 30% vs vehicle; p<0.05), an effect blocked by EHT1864 and tempol. E2 also increased H2O2 generation (152 ± 4%; p<0.05). Thioredoxin, NQ01 and peroxiredoxin1 (71 ± 6%; 78 ± 9%; 69 ± 8%; p<0.05 respectively) levels were decreased by E2 as was PCNA expression (72 ± 2%; p<0.05). 16αOHE1 exhibited a rapid (5 min) and exaggerated increase in ROS production (355 ± 41%; p<0.05), blocked by tempol and EHT1864. This was associated with an increase in Nox4 expression (139 ± 11% vs vehicle, p<0.05). 16αOHE1 increased BACH1, (129 ± 3%; p<0.05), a competitor of Nrf2, which was decreased (92 ± 2%). In contrast, thioredoxin expression was increased by 16aOHE1 (154 ± 22%; p<0.05). PCNA (150 ± 5%) expression was also increased after exposure to 16αOHE1. In conclusion, E2 and 16αOHE1 have differential effects on redox processes associated with PASMC growth. Whereas E2 stimulates ROS production in a slow and sustained manner without effect on cell growth, 16αOHE1 upregulates Nox4 with associated rapid increase in ROS generation and downregulation of antioxidant systems, affecting proliferation. Our findings suggest that E2 -derived metabolites may promote a pro-proliferative PASMC phenotype through Nox4-derived ROS generation. These deleterious effects may impact on vascular remodeling in PAH.
Abstract 307: The Presence of an Adrenergic System in Perivascular Adipose Tissue
Authors: Ayala-Lopez Nadia , Jackson William F , Wilson James N , Burnett Robert , Martini Marisa , Frimodig Kristian , Fink Gregory D , Watts Stephanie W
Published: July 2021

Perivascular adipose tissue (PVAT) is under recognized for its importance in blood pressure regulation. Visceral adipocytes reportedly contain catecholamines. Adipocytes in PVAT are directly adjacent to the blood vessels they surround and therefore the production, release and/or reuptake of catecholamines may significantly affect vascular tone. We hypothesize that an adrenergic system is present in PVAT. Glyoxylic acid staining revealed the presence of catecholamines in the cytosol of mesenteric PVAT adipocytes. Dopamine (DA), norepinephrine (NE) and epinephrine were quantified by HPLC in rat aortic PVAT, brown fat, mesenteric PVAT and retroperitoneal fat with NE being the most abundant at concentrations of 731.9, 815.0, 668.7 and 73.2 ng/g from each tissue, respectively. Two key enzymes in catecholamine synthesis; tyrosine hydroxylase and dopamine β-hydroxylase, were located to PVAT adipocytes by immunohistochemistry. The norepinephrine transporter (NET) was detected on mesenteric PVAT adipocytes by confocal microscopy using ASP+ (2μM), a fluorescent NET substrate. Uptake of ASP+ was blocked by the NET specific inhibitor nisoxetine (10μM) (see figure). These data show that PVAT contains all of the elements of an adrenergic system and may contribute to vascular and adipose function in health and disease.
Abstract 372: Upregulation of the Mineralocorticoid System in Obesity-associated Diabetes Leads to Increased Adipocyte Rho Kinase Activation and Dysregulation of Adipocytokines
Authors: Nguyen Dinh Cat Aurelie , Callera Glaucia E , Antunes Tayze T , Montezano Augusto C , He Ying , Jenkins Carol , Touyz Rhian M
Published: July 2021

Increased activation of the renin-angiotensin-aldosterone (RAAS) system is often associated with obesity and metabolic syndrome. We previously reported that aldosterone (aldo) produced by adipocytes regulate vascular function. Despite the fact that aldo production by adipocytes is increased in obesity, the role of aldo and its receptor, the mineralocorticoid receptor (MR), in the regulation of adipocytes biology and their downstream signaling remain elusive. Since Rho kinase (Rock) signaling has recently been implicated in the development of obesity, we tested the hypothesis that MR upregulation leads to dysregulation of adipokines through Rock-dependent mechanisms in obesity. Here we used obese db/db and lean db/+ mice, treated for 4 weeks with K canrenoate (MR antagonist, 30 mg/kg/day) and fasudil (Rock inhibitor, 30 mg/kg/day). Aldo production and Rock activation were measured by ELISA. mRNA and protein levels of adipokines and Rock signaling were assayed by real time PCR and immunoblotting. Plasma and adipocyte-derived aldo levels were increased in db/db mice (plasma: pg/mL, db/+ 310±33, db/db 567±43, p<0.05; adipocytes: pg/mL/μgRNA, db/+ 329±130, db/db 3125±494, p<0.002), an effect partially prevented by MR blockade (pg/mL/μgRNA: db/db 1278±176, p<0.01) and not by fasudil. Aldosterone synthase mRNA levels were increased (2.3 fold) as well as
Nr3c2
(MR) (1.8 fold) and markers of MR activation (
Sgk1
and
Ngal
- 2.3 and 2.9 fold) in mature adipocytes from db/db mice. In mature adipocytes from db/db, adiponectin mRNA levels were decreased (2.6 fold; p<0.01), whereas leptin and IL-6 mRNA levels were increased (2 and 4.8 fold; p<0.01). All changes were blocked by K canrenoate. Rock activity and downstream effectors, such as activation of MYPT1 and ERM, were increased in perivascular adipose tissue from db/db mice, an effect prevented by MR blockade. In conclusion, our data demonstrate that in db/db mice adipocyte MR-dependent activation of Rock is associated with a pro-inflammatory adipose phenotype that is normalized by MR blockade. Our results implicate a potential role of adipocyte aldo/MR through RhoA/Rock in adipocyte dysfunction in obesity/diabetes, important co-morbidities often associated with metabolic syndrome and hypertension.
Abstract 374: EET Agonist Improves Cardiac Energy Metabolism and Heart Function by Regulating Fatty Acid Oxidation and Oxidative Stress in Infarcted Myocardium
Authors: Cao Jian , Peterson Stephen J , Favero Gaia , Rezzani Rita , Fabrizio Rodella Luigi , Schwartzman Michal L , Zeldin Darryl C , Shapiro Joseph , Abraham Nader G
Published: July 2021

Introduction:
Myocardial Ischemia (MI), one of the major causes of heart failure, is associated with cardiac remodeling, insufficient angiogenesis and enhanced oxidative stress. Cytochrome P450 epoxygenase metabolites of arachidonic acid, EETs, have multiple cardiovascular effects, including vasodilation, inhibition of inflammatory response and stimulation of epithelial cell growth. In addition, emerging studies indicate a role of these unique lipid mediators in the regulation of metabolic homeostasis. We propose that EET agonists reduce post infarcted cardiac remodeling by improving cardiac dysfunction through increased angiogenesis improved cardiac energy metabolism and a reduction in oxidative stress.

Methods:
C57B16 mice were divided into 3 groups: sham, mice with myocardial infarction (MI) via LAD ligation and mice with MI treated with an EET-agonist (NUDSA). NUDSA was administered after 5 days of MI (0.5 mg/kg) in C57B16 mice. Myocardial echocardiography was performed 30 days after MI to assess the cardiac function. Capillary density, oxidative stress and cardiac energy metabolism markers were compared among the groups.

Results:
Echocardiography showed that left ventricle dilatation, measured as end diastolic area (EDA), was reduced in NUDSA treated groups compared to the MI group (C57, EDA: MI: 0.413 ±0.02 cm
2
; MI+NUDSA: 0.217±0.03 cm
2
; p<0.05). Cardiac Index, decreased by MI, was restored by NUDSA in C57 mice. Cardiac histological examination revealed an increase in myocardial angiogenesis and capillary density in mice treated with NUDSA (p<0.01 vs. MI). Cardiac tissue showed an increased expression of ETS-1, phosphorylated Acetyl CoA Carboxylase (pACC) and Carnitine Palmitoyl Transferase I (CPT-1) along with a decrease in 3NT and gpphox 91 expression in mice treated with NUDSA as compared to the MI group (p<0.05).

Conclusion:
This is the first study to demonstrate that EET improves cardiac energy metabolism in infarcted heart by regulating fatty acid oxidation and ameliorating oxidative stress and cardiac remodeling. Thus pharmacological induction of EET may open new avenues in the treatment of patients with post infarcted heart failure.
Abstract 375: A New Mouse Model to Characterize the Mechanisms of Endothelin-1-Induced Vascular Injury
Authors: Coelho Suellen C , Rautureau Yohann , Rehman Asia , Paradis Pierre , Schiffrin Ernesto L
Published: July 2021

Objective:
To develop a model permitting the study of the mechanisms of endothelin (ET-1)-induced vascular injury, we generated an inducible and endothelial cell (EC)-restricted human ET-1 (
EDN1
) cDNA overexpressing transgenic mouse, which would accordingly be devoid of developmental effects.

Methods and Results:
A transgene was engineered that expresses chloramphenicol acetyltransferase (
cat
) cDNA prior to Cre-mediated excision, and
EDN1
cDNA after Cre-mediated excision, under the control of cytomegalovirus immediate early enhancer/chicken β-actin promoter (CAG). Co-transfection of Cre expression vector and pCAG-
cat
-
EDN1
caused a 30-fold increase in ET-1 production evaluated by ELISA. A DNA fragment containing the CAG-
cat
-
EDN1
transgene was used to generate transgenic mice. PCR genotyping demonstrated that 14/132 mice were transgenic. Two of 7 transgenic lines were selected based on cardiac
cat
expression level, which were twice higher in line C-134 than C-170. Inducible EC-restricted
EDN1
mice were generated crossing CAG-
cat
-
EDN1
mice with mice expressing Cre recombinase fused to a tamoxifen (TAM)-inducible modified estrogen receptor ligand binding domain (
Cre
ER
T2
) under control of EC-specific receptor tyrosine kinase (
Tie2
) promoter. To investigate the extent of CreER
T2
activation by TAM and tissue specificity,
Tie2
-CreER
T2
mice were crossed with
ROSA
mT-mG/mT-mG
reporter mice expressing a membrane-targeted tandem dimer
tomato
(mT) before Cre-mediated excision, and membrane-targeted enhanced green fluorescent protein (mG) after excision.
Tie2
-CreER
T2
/
cat
-
EDN1
and
Tie2
-CreER
T2
/
ROSA
mT-mG/+
mice were treated with 1 mg TAM/d SC for 5 d and sacrificed 14-16 d later. mG expression was detected in 22±3% of mesenteric artery EC of
Tie2
-CreER
T2
/
ROSA
mT-mG/+
mice. Plasma ET-1 levels were similar in vehicle-treated
Tie2
-CreER
T2
/
cat
-
EDN1
(1.2±0.1 pg/mL, n=4) and wild-type mice (1.1±0.1 pg/mL, n=2), demonstrating no leaky expression. TAM induced 8-fold increase in plasma ET-1 levels in
Tie2
-CreER
T2
/
cat
-
EDN1
mice (9.1 ± 0.3 pg/mL, n = 4).

Conclusion:
Tie2
-CreER
T2
/
cat
-
EDN1
-inducible EC-restricted
EDN1
overexpressing mice allow the study of ET-1 vascular effects in adult independently of developmental effects.
Abstract 383: Hypertensive and Renal Injury Responses to Angiotensin II and High Salt Intake in Mice Lacking the Gene for Interleukin-10
Authors: Singh Purnima , Castillo Alexander , Majid Dewan S
Published: July 2021

Endogenous interleukin-10 (IL-10) exerts immune down-regulating action on the generation of tumor necrosis factor-alpha (TNF-α). The present study examined the hypothesis that IL-10 plays a protective role in hypertension and renal injury induced by angiotensin II (AngII) and high salt (HS) diet by minimizing TNF-α production. Systemic blood pressure (BP; monitored by implanted radio-telemetry), TNF-α level in plasma and in the kidney (by ELISA) as well as renal injury (glomerulosclerosis, GS by PAS staining and renal interstitial fibrosis, RIF by Trichrome staining) responses to chronic infusion of AngII (400 ng/min; osmotic minipump) for 2 wks were evaluated in wild-type (WT; n=11) and IL-10 gene knockout mice (KO; n=11) which were fed either normal (NS; 0.03% NaCl, n=5) or HS (4% NaCl; n=6) diets. On the last day of the experiment, a 24 hr urine collection was made using metabolic cages prior to sacrificing the mice for the collection of plasma and renal tissue samples. The mean baseline BP in KO was lower (104±3 vs 116±4 mmHg) than that in WT. Increase in BP in AngII+HS treated KO was lower (Δ 20±5 vs Δ 39±2 mmHg) than that in WT but similar in AngII+NS treated KO and WT (Δ 40±3 vs Δ 47±7 mmHg). In AngII+HS treated WT, TNF-α was higher in plasma (69±6 vs 34±4 pg/mL) and in renal tissue (208±15 vs 95±11 pg/mg protein) compared to values in WT treated with AngII+NS. In AngII+HS treated KO, TNF-α was lower in plasma (20±3 vs 180±44 pg/mL) and in renal tissue (205±23 vs 277±23 vs pg/mg protein) compared to values in KO treated with AngII+NS. The urinary nitrate/nitrite excretion rate was higher in AngII+NS (0.56±0.25 vs 0.08±0.01 mM/24 hr) and AngII+HS (1.23±0.12 vs 0.18±0.02 mM/24 hr) treated KO compared to the correspondingly treated WT. The eNOS protein expression was higher in KO treated with AngII+NS (~2 folds) or AngII+HS (~3 folds) compared to those in treated WT. GS (24.6±1.3 vs 13.8±2.1 %) and RIF (10.6±1.1 vs 7.8±0.5 %) changes were greater in AngII+NS treated KO than those in treated WT. However, the changes were minimal in HS treated groups. In conclusion, these data demonstrate that there exists an interaction of IL-10 and eNOS activity in the regulation of TNF-α in the kidney that provides a protective role by minimizing hypertension and renal injury induced by Ang II and HS intake.
Abstract 39: Cyp4a1 Transgenic Rats Generated Using Sleeping Beauty Transposon System Restores the Impaired Myogenic Responses in the Afferent Arteriole of Dahl S Rats
Authors: Fan Fan , Ge Ying , Murphy Sydney , Geurts Aron M , Jacob Howard , Roman Richard J
Published: July 2021

We have reported that the production of 20-HETE is reduced in the renal vasculature of Dahl S rats and that myogenic and TGF responses of afferent arteries (Af-Art) are impaired in Dahl S rats. In this study we generated CYP4A1 transgenic rats in the Dahl S inbred strain background utilizing the enhanced
Sleeping Beauty
(SB100X) transposon system to determine if upregulation of 20-HETE production can restore vascular reactivity and oppose the development of renal injury. Fertilized eggs collected from female Dahl S rats were microinjected with a transposon vector harboring the rat CYP4A1 cDNA under the control of the ubiquitous CAG promoter along with SB100X transposase mRNA to produce transgenic founders. Heterozygous founders were backcrossed to Dahl S rats, transgene insertion sites were identified by Ligation Mediated PCR and sequencing, and the progeny were brother-sister mated to derive homozygous transgenic lines. The expression of CYP4A protein was significantly elevated and the production of 20-HETE was 3-fold higher in the renal outer medullary tissue of CYP4A1 transgenic (n=17) compared to Dahl S rats (n=17). 20-HETE production was 10-fold higher in renal microvessels of CYP4A1 transgenic animals than Dahl S rats. (0.2±0.3, n=22 versus 1.9±0.1 pmol/mg/min, n=14). The luminal diameter of the Af-Art decreased significantly from 15.9 ± 0.6 to 14.1 ± 0.5 μm in CYP4A1 transgenic rats (n=5) when the perfusion pressure was increased from 60 to 120 mmHg, whereas it remained unaltered in Dahl S rats (from 19.4 ± 2.3 to 20.6 ± 5.6 μm, n=22). These studies further support the view that a deficiency in the formation of 20-HETE in the renal microcirculation contributes to the marked susceptibility of Dahl S rats to develop of hypertension and diabetic induced renal injury, and the new CYP4A1 transposon transgenic rat model may be useful for determining the mechanisms involved.
Abstract 393: Chronic Nebivolol Treatment Attenuates MMP Activity and Oxidative Stress and Improves Renovascular Hypertension-induced Cardiac Hypertrophy
Authors: Sanchez Elen R , Ceron Carla S , Gimaraes Danielle A , Prado Cibele M , Martins-Oliveira Alisson , Rossi Marcos A , Gerlach Raquel F , Tanus-Santos Jose Eduardo
Published: July 2021

Nebivolol (Nebi) is the most selective cardiac β1-adrenergic receptor blocker and exerts antioxidant effects. Reactive oxygen species (ROS) enhance cardiac matrix metalloproteinase activity (MMPs) and contribute to hypertension-induced left ventricular hypertrophy (LVH). However, it is uncertain whether Nebi decreases MMP-2 levels and cardiac remodeling associated with hypertension as a result of its antioxidant properties. Hypertension was induced by clipping the left renal artery (2K1C). Six weeks after surgery, hypertensive and sham rats were treated with Nebi, Metoprolol (Meto) or Vehicle (by gavage) for four weeks. Systolic blood pressure (SBP) was monitored weekly by tail-cuff plethysmography. LV structural changes were studied in hematoxylin/eosin sections. MMP levels and activity were determined by immunofluorescence and in situ zymography. ROS and nitrotyrosine levels were evaluated by dihydroethidium and immunohistochemistry, respectively. Similar reduction in SBP was found with both treatments (202±5 mmHg in 2K1C+Vehicle versus 161±19 and 162±18 mmHg in 2K1C Nebi or Meto groups, respectively; P<0.05). Both treatments reduced LV remodeling and ROS formation (P<0.05). Both drugs decreased nitrotyrosine levels (3.9±0.2, 2.3±0.3, and 2.4±0.3 arbitrary units, respectively in 2K1C+vehicle, 2K1C+Meto, and 2K1C+Nebi groups, respectively; P<0.05). Increased MMP-2 levels (16.0±2.0 versus 7.0±0.9 arbitrary units; P<0.05) and activity (8.0±0.4 versus 6.0±0.1 arbitrary units; P<0.05) were observed in the 2K1C+vehicle group when compared to the sham group. These alterations were normalized by both treatments (similar levels to those found in the sham group). No significant changes were observed in the sham groups. These findings suggest that different β-blockers exert important antioxidant effects that may underlie the lower LV MMP activity and cardiac remodeling in 2K1C hypertension.
Abstract 394: Angiotensin II Mediated Increase in Hypertension and Cardiac Hypertrophy in MyD88 Knockout Mice
Authors: Singh Madhu V , Harwani Sailesh C , Whiteis Carol A , Cicha Michael Z , Chapleau Mark W , Abboud Francois M
Published: July 2021

Toll-like receptors (TLR) are a class of pattern-recognizing receptors (PRR) that play a central role in the innate immune response during infection and sterile injury. MyD88 is an adapter protein that mediates the majority of TLR responses. Since inflammation is a coexisting condition in several cardiovascular diseases, TLRs are thought to play a major role in these conditions. We have previously shown that indeed post-MI survival was significantly improved and cardiac fibrosis and hypertrophy were reduced in MyD88-/- mice (Singh et al. 2012. JMCC). In this study we tested whether angiotensin II (AngII) hypertension and cardiac hypertrophy depended on TLR signaling pathways mediated by MyD88. Male MyD88-/- mice and C57BL/6 mice of 10 to 12 weeks of age were subcutaneously implanted with osmotic minipumps (Alzet) eluting saline or AngII (Sigma, 733 ng/kg/min). Tailcuff pressures were measured with BP2000 (Visitech Systems). Mice were sacrificed after 3 weeks of AngII infusion and hearts were collected for weighing and gene expression analyses. In control WT mice, mean arterial pressure (MAP) remained near baseline levels during the first week of infusion averaging 71± 2 mm Hg and then increased to an average of 100 ± 3 mm Hg and 102 ± 2 mm Hg during the 2nd and 3rd weeks of infusions, respectively. In MyD88-/- mice, MAP increased from a baseline of 84 ± 3 to a high of 120 ± 7 mm Hg during the first week and then declined to 109 ± 6 and 91 ± 9 mm Hg during the 2nd and 3rd weeks. The heart weight to body weight ratios (HW/BW x 1000) after 3 weeks of AngII infusion were not significantly different between WT (5.23 ± 0.15) and MyD88-/- (4.76 ± 0.16). Increases in cardiac hypertrophic marker gene Acta1 were up 4-fold in both WT and MyD88-/- mice, and increases in proinflammatory TNF-alpha, IL-1β, and Nox4 were seen in both genotypes, but the increase in TNF-alpha was significantly greater in MyD88-/- mice.

We conclude that unlike post- MI cardiac hypertrophy, the AngII cardiac hypertrophy is not MyD88 -dependent, yet the delayed Ang II pressor response is abrogated in the absence of MyD88. The delayed pressor response to AngII infusion is likely dependent on the immune system.
Abstract 400: Angiotensin II Triggers the Same Pressor Mechanisms in Salt-sensitive Hypertension and During Salt Depletion
Authors: Blaustein Mordecai P , Chen Ling , Li Meng , Gao Junjie , Hamlyn John M
Published: July 2021

Salt restriction or blood volume decline activates the renin-angiotensin (Ang) system to protect against short- and long-term drops in blood pressure (BP). Excess dietary salt and salt retention, however, activates CNS Ang II-mediated mechanisms that elevate BP. We tested the idea that the same CNS-regulated downstream mechanisms modulate total peripheral vascular resistance (TPR) under both conditions. Protocol 1: normal Sprague-Dawley (SD) rats were fed either normal salt (NS, 0.4% NaCl) or low salt (LS, 0.1% NaCl) for 2 wks. Protocol 2: SD rats were infused subcutaneously with vehicle (V, saline) or Ang II (A, 150 ng/kg/min); some V and some A rats were fed NS, and the others were fed high salt (HS, 2% NaCl) for 2 wks. At the end of both protocols, intra-arterial BP was recorded and blood was drawn for endogenous ouabain (EO) determination by radioimmunoassay and multi-stage mass spectroscopy. Aortae and mesenteric arteries were harvested for protein immunoblots to determine arterial smooth muscle (ASM) expression of Na/Ca exchanger-1 (NCX1), a key Ca
2+
transporter. LS did not affect mean BP (87±2 vs 91±4 mm Hg,
n
=6 each), but did raise plasma EO (0.70±0.19 vs 0.21±0.02 nM, P
<
0.05) and increase ASM NCX1 expression 1.52-fold. Ang II infusion and, especially, HS + Ang II, increased mean BP (110±4 and 124±3 mm Hg,
P
<0.05 and
P
<0.001, respectively, vs 100±4 mm Hg,
n
=5-8) and plasma EO (0.53±0.31 and 1.31±0.72 nM, respectively, both P<0.05, vs 0.07±0.02 nM,
n
=5-8). HS + Ang II also increased ASM NCX1 expression 1.91-fold. HS + Ang II, as well as LS also increased expression of SERCA2 and TRPC6, two other ASM Ca
2+
transporters. Intracerebroventricular Ang II also raises plasma EO and increases expression of the 3 Ca
2+
transporters in ASM; thus, the CNS controls this pressor pathway (Hamlyn et al.,
Hypertension
60
(3, Suppl.):e419, 2012). The new data reveal that
both
LS and HS activate the same downstream mechanisms: they elevate plasma EO and ASM Ca
2+
transporter expression. The increases in ASM Ca
2+
transporter expression, and enhanced sympathetic drive, should increase arterial tone and raise BP during salt excess, and minimize BP decline. We conclude that these fundamental mechanisms contribute to “whole body autoregulation” in the long-term control of TPR and BP.
Abstract 409: The Association Between Carotid Artery Plaqus and Cardiovascula Risk Factor in Japanese Individuals
Authors: Arita Mikio , Tanaka Hiroto , Takahashi Maasa , Nagano Shiori , Sasabe Keiko , Yamamoto Mio
Published: July 2021

Introduction:
Patients with many cardiovascular risk factors develop the carotid artery plaques(CAP) at the early atherosclerotic change. In this study, we performed the comparison between the individuals with CAP and without CAP and investigated the characteristics of cardiovascular risk factors.

Subjects and methods:
A total of 310 individuals matched-age(mean age 67.6± 3.7 years) underwent the comprehensive health examination such as Body mass index(BMI), AIP75, blood pressure(BP), Sodium ingestion, Pulse wave velocity(PWV) and serum data. Carotid artery ultrasound was done to all individuals and CAP and the intima-media thickness(IMT) were shown.

Results:
The prevalence of CAP was 20%(62/310) and that of CAP in men and women was 24.6%(35/142) and 16.1%(27/168), respectively. PWV and IMT of the individuals with CAP (CAP group) was significantly higher, compared with those without CAP (not CAP group). BMI and sodium ingestion of CAP group was significantly lower, compared with those of not CAP group. In addition, systolic BP and G-GTP of CAP group showed the high tendency (p=0.085, p=0.056, respectively) and diastolic BP and HDL-C of CAP group showed the low tendency (p=0.097, p=0.052, respectively), compared with those of not CAP group. PWV of CAP group in man was significantly higher, compared with that of not CAP group in man. However, HDL-C of CAP group in woman showed the low tendency, compared with that of that of not CAP group in woman.

Conclusion:
It has been suggested that the development of CAP is associated with the cardiovascular risk factor such as PWV, IMT, HDL-C , G-GTP and BP.
Abstract 414: Adipose Angiotensin AT2 Receptors Modulate Thermogenesis Though Interactions with Epidermal Growth Factor Signaling
Authors: Keen Henry L , Littlejohn Nicole K , Liu Xuebo , Grobe Justin L , Sigmund Curt D
Published: July 2021

The brain renin-angiotensin system (RAS) stimulates resting metabolic rate (RMR) in part through a mechanism involving suppression of the circulating RAS. This effect appears to be mediated through the loss of tonic adipose angiotensin AT2 receptor (AT2R) activation specifically within inguinal fat. Mice with hyperactivity of the brain RAS (“sRA” mice, expressing human renin via the synapsin promoter and human angiotensinogen via its own promoter) and littermate controls were chronically infused with vehicle or the AT2R agonist, CGP-42112a (CGP, 90 ng/hr, 8 wk, sc). To identify altered signaling pathways in sRA mice and their response to CGP treatment, total RNA was isolated from inguinal adipose tissue and transcript abundance was quantitated by RNA-Seq (50 bp paired reads sequenced with the Illumina HiSeq 2000). There was a significant (P<0.001) change in expression of 123 genes in sRA mice (n=3) compared to littermate controls (n=3), which were generally reversed by CGP treatment (n=4). By manual inspection, we observed that 51 of these genes are associated with epidermal growth factor (EGF) signaling. Consistent with this, Gene Set Enrichment Analysis of the RNA-Seq data demonstrated that genes in the EGF receptor signaling pathway were, as a group, statistically upregulated (P=0.02) in sRA and suppressed (P=0.02) by CGP treatment. Therefore, to further explore the impact of increased EGF signaling on RMR and to isolate a potential modulatory effect of AT2R activation on this response, wildtype C57Bl/6J male mice (9 wk) were infused with EGF (833 ng/hr, 2 wk, sc) with or without co-infusion of CGP. This brief EGF infusion caused a possible increase in RMR (vehicle n=20, 0.173 ± 0.009; EGF n=20, 0.192 ± 0.012 kcal/hr, P=0.13), which was significantly reduced with co-infusion of CGP (90 ng/hr, 2 wk, sc) (EGF+CGP n=17, 0.165 ± 0.005, P<0.05 vs EGF alone; CGP alone n=9, 0.156 ± 0.010). Together these data implicate elevated EGF signaling in the elevated RMR of mice with elevated brain RAS activity. Further, these data suggest a suppressive effect of AT2R activation upon RMR specifically in the context of elevated EGF signaling. Studies utilizing primary inguinal adipose cultures are underway to investigate the molecular basis of the EGF-AT2R interaction.
Abstract 433: Renal Effects of Everolimus Versus Bone Marrow-derived Stem Cells in Rat Model of Glomerulonephritis
Authors: Elmarakby Ahmed A , Pye Chelsey , Baban Babak , Zedan Mohamed M , Bakr Ashraf
Published: July 2021

The progression of renal disease is mainly influenced by degree of glomerular endothelial injury and effectiveness of glomerular endothelial repair. Considerable research efforts have recently been undertaken to examine glomerular endothelial repair by progenitor cells. We hypothesize that bone marrow-derived stem cells (BMDSCs) ameliorate experimental glomerulonephritis by restoring glomerular endothelial barrier function through improving the repair process. Anti-Thy1-glomerulonephritis was induced in Sprague Dawley rats by a single injection of an antibody against Thy1, which is mainly expressed on glomerular mesangial cells. Rats were then treated with the immunosuppressant everolimus (EV) daily or injected with isolated BMDSCs after one week of injection of anti-Thy1. After nine days of Injection of anti-Thy1, glomerular albumin permeability and albuminuria were significantly increased when compared to control group (P< 0.05). EV was superior than BMDSCs in attenuating the increase in glomerular albumin permeability and albuminuria in anti-Thy1 injected rats. However, only EV treatment significantly reduced the markers of glomerular injury, nephrinuria and podocalyxin excretion levels in anti-Thy1 injected rats (nephrinuria was 0.4± 0.1 vs. 0.8± 0.02 mg/day and podocalyxin excretion was 7± 1 vs. 11± 1 μg/day in EV treated vs. untreated anti-Thy1 injected rats, P< 0.05). Anti-Thy1 injected rats also showed hypercellular glomeruli with loss of Bowman space and variable number of lymphocyte and EV treatment partially restored these pathophysiological changes whereas BMDSCs had no significant effect. EV treatment also reduced number of renal CD3+ and macrophage and lowered IL-17 and caspase 3 levels in the anti-Thy1 injected rat kidneys. These data suggest that EV early treatment preserve glomerular endothelial barrier function in Anti-Thy1-induced glomerulonephritis via anti-apoptotic and anti-inflammatory mechanisms.
Abstract 438: Rapid Inhibition of Pre-sympathetic Kidney-related Neurons in the Rostral Ventrolateral Medulla by Leptin
Authors: Gao Hong , Barnes Maria J , Majid D.S. Safwan , Derbenev Andrei V
Published: July 2021

The adipocyte-derived hormone leptin regulates satiety and plays a vital role in energy homeostasis. Several lines of evidence suggest that obesity is associated with increased prevalence of hypertension and accountable at least in part for the elevation of sympathetic nerve activity. Neurons in the rostral ventrolateral medulla (RVLM) are critical components of both the sympathetic nervous system and cardiovascular regulation. By using whole-cell patch-clamp recordings in brainstem slices we tested the hypothesis that leptin suppresses activity in pre-sympathetic kidney-related RVLM neurons. Application of leptin caused a rapid membrane hyperpolarization in 43% of recorded kidney-related RVLM neurons. Out of 14 neurons, leptin (500nM) hyperpolarized 6 neurons (from -53.3±3.5 mV to -57.0± 3.2 mV; P<0.05) and had no effects on the rest of the neurons. The input resistance was significantly increased by leptin in 6 out of 14 RVLM kidney-related neurons from 276±92 MΩ to 336±97 MΩ (P<0.05). Moreover, leptin (500nM) reduced the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) from 7.9±2.1 Hz to 5.5±2.3 Hz (P<0.05; n=5) with an average of 36% decrease without changing sEPSCs amplitude. The frequency and amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs) was not affected by administration of leptin. Our study demonstrates that leptin directly hyperpolarized the kidney-related RVLM neurons and indirectly suppressed excitatory synaptic activity to pre-sympathetic kidney-related RVLM neurons. This work was supported by P30GM103337.
Abstract 439: Role of Hindbrain Endogenous Melanocortin Receptor Activity in Contributing to Hypertension in SHR
Authors: do Carmo Jussara M , da SIlva Alexandre A , Wang Zhen , Hall John E
Published: July 2021

We previously demonstrated that activation of the central nervous system (CNS) melanocortin system plays a key role in the modulation of sympathetic nerve activity (SNA) and blood pressure (BP) regulation. In the present study, we examined whether chronic inhibition of melanocortin-4 receptors (MC4R) in the hindbrain attenuates the elevated blood pressure in spontaneously hypertensive rats (SHR). The long-term cardiovascular and metabolic effects of MC4R antagonism were assessed in SHR and normotensive Wistar-Kyoto (WKY) rats. Male WKY rats (n=6) and SHR (n=7) were implanted with telemetry probes to measure BP and heart rate (HR) 24-hrs/day, and an intracerebroventricular (ICV) cannula was placed into the fourth ventricle (4
th
V). After 10 days of recovery and 5 days of control measurements, the MC4R antagonist (SHU-9119, 1 nmol/h, 4
th
V) was infused for 10 days followed by a 5-day recovery period. Chronic hindbrain MC4R antagonism significantly increased food intake and body weight in WKY (17±1 to 35±2 g/day and 280±8 to 353±8 g) and SHR (19±2 to 35±2 g/day and 323±7 to 371±11 g). No changes were observed in blood glucose levels (99±4 to 87±4 and 89±5 to 89±4 mg/dl, respectively for WKY and SHR). Chronic SHU-9119 infusion reduced MAP and HR similarly in WKY (-5±1 mmHg and -47±3 bpm) and SHR (-8±3 mmHg and -44±3 bpm). These results suggest that although hindbrain MC4R activity is important for appetite and HR regulation, it does not play a major role in mediating the elevated blood pressure in SHR. (NHLBI-PO1 HL51971/AHA SDG5680016)
Abstract 441: Aldosterone-salt Hypertension Depends on the SFO, Central Aldosterone Synthase and MR Specifically in the PVN
Authors: Huang Bing S , Ahmad Monir , Chen Aidong , White Roselyn A , Leenen Frans H , Leenen Frans H
Published: July 2021

Central blockade of mineralocorticoid receptor (MR) prevents aldosterone (aldo)-salt induced hypertension. We examined the role of the subfornical organ (SFO), aldo synthesized locally in the brain, and MR specifically in the paraventricular nucleus (PVN) in aldo-salt hypertension. Wistar rats with telemetry probes were treated with chronic intra-cerebroventricular infusion of aldo synthase (AS) inhibitor FAD286 (25 μg/day), MR blocker eplerenone (5 μg/day) or vehicle. After 2 days, subcutaneous (sc) aldo infusion (1 μg/h) was started and saline was provided as drinking water. In a second set of rats with telemetry, electrolytic or sham lesions of the SFO, or bilateral intra-PVN infusion of AAV-MR-siRNA or AAV-SCM-siRNA (1 μl of 5x10
10
genomic particles/ml) at 100ng/min were performed, and sc aldo infusion started 1 week later. AAV-MR-siRNA decreased MR mRNA and protein expression in the PVN by ~60 and 30%, but had no effects on MR expression in other nuclei such as the SFO and SON. SFO lesion, blockade of brain AS or MR, or knockdown of MR in the PVN attenuated aldo-salt hypertension by ~60%.

Data=means± SE (n=5-9/group). *p<0.05, vs. others, a:p<0.05, vs. vehicle or sham lesion.

These results suggest that an increase in circulating aldosterone may via MR and AT
1
R in the SFO increase local aldosterone production in hypothalamic nuclei such as the SON and PVN, and via MR in the PVN activate a central aldosterone-MR-AT
1
R neuro-modulatory pathway, which plays a major role in the progressive hypertension.

(Supported by grant # FRN:MOP-74432 from the Canadian Institutes of Health Research)
Abstract 447: Intracerebroventricular Administration of Autologous Bone Marrow-derived Cells Attenuates Sympathetic Hyperactivity in Deoxycorticosterone Acetate-salt Hypertensive Rats
Authors: Yamazato Masanobu , Nakamura Takuto , Ishida Akio , Yamazato Yoriko , Ohya Yusuke
Published: July 2021

Objectives:
Administration of deoxycorticosterone acetate (DOCA) in combination with salt loading and surgical removal of one kidney induces hypertension. Central mechanism is involved in this hypertension. Bone marrow-derived cells (BMCs) include mesenchymal stem cells play critical role in repairing damaged tissue and anti-inflammation. We hypothesized that increase in number of BMCs in the brain would attenuate the DOCA-salt hypertension.

Methods:
Sprague-Dawley rats underwent unilateral nephrectomy were divided into following 4 groups: rats received sham treatment with intracerebroventricular (icv) administration of medium (S/M group, n=5); rats received sham treatment with icv administration of BMCs (S/B group, n=5); rats received DOCA-salt treatment with icv administration of medium (D/M group, n=4); rats received DOCA-salt treatment with icv administration of BMCs (D/B group, n=7). Three weeks following the initiation of DOCA-salt treatment, rats had surgery to implant arterial and venous catheters. Resting mean arterial pressure (MAP) of rats was recorded in conscious unrestrained state and resting sympathetic tone was evaluated with a peak depressor response produced by hexamethonium (C6) injection.

Results:
Resting MAPs of S/M, S/B, D/M and D/B group were 116±4, 120±5, 194±4, 172±9 mmHg, respectively. DOCA-salt treatment significantly increased MAP in both D/M and D/B group. D/B group tended to have lower MAP than D/M group, however, post hoc analysis did not reach significant. The peak depressor responses to C6 injection in S/M, S/B, D/M and D/B group were 41±2, 46±5, 97±10, 69±5 mmHg, respectively. DOCA-salt treatment significantly increased the peak depressor response to C6 and icv administration of BMCs attenuated the increase in peak depressor response.

Conclusion:
BMCs in the brain may have protective role against sympathetic hyperactivity caused by DOCA-salt treatment.