Abstract P619: A Comparison of the Adrenergic System within the Perivascular Adipose Tissue in Two-High Fat Fed Models of Obesity-induced Hypertension: Dahl S and Sprague-Dawley Rats

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Nadia Ayala-Lopez ◽  
Hannah Garver ◽  
Kyan Thelen ◽  
Robert Burnett ◽  
Andres Contreras ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Organic Cation Transporter ◽  
The Body ◽  
Monoamine Oxidase A ◽  
Adrenergic System ◽  
Sprague Dawley ◽  
High Fat ◽  
Perivascular Adipose Tissue ◽  
Sd Rats ◽  
Induced Hypertension

Increased sympathetic activity is one cause of obesity-induced hypertension. Over-activity of an adrenergic system in mesenteric perivascular adipose tissue (MPVAT) could contribute to high BP given its close proximity to splanchnic arteries and veins. We tested the hypothesis that high fat (HF) fed models of obesity-induced hypertension have elevated norepinephrine (NE) in MPVAT, increasing exposure of arteries to NE. Male Dahl S and Sprague-Dawley (SD) rats were fed a HF (60% fat, 0.3% NaCl; kcal) or a normal fat diet (NF; 10% fat, 0.25% NaCl; kcal) from weaning age (n=5). At 20-29 weeks of age, rats were sacrificed and tissues collected (all results shown in the table). HF increased the body weight of Dahl but not SD. Total fat mass was increased in the HF vs NF rats of both models. Mean arterial BP measured by radiotelemetry was elevated in the Dahl S HF vs NF and slightly elevated in the SD HF vs NF rats. Plasma NE was not elevated in either model. Surprisingly, MPVAT had significantly less NE in the Dahl S HF vs NF but was not altered in the SD. Expression of genes involved in NE synthesis, uptake and metabolism was measured by PCR to determine whether the MPVAT’s adrenergic system was altered in HF rats. Tyrosine hydroxylase ( Th ) mRNA was not detected in the Dahl S (SD not measured). Expression for the NE metabolizing enzymes monoamine oxidase-A (MAO-A) and catechol-o-methyl transferase ( Comt ) was not different. However, S lc22a3 mRNA (organic cation transporter 3) was reduced in the SD HF vs NF rat. These data reveal that the elevation in BP in Dahl S and SD rats fed a HF diet may be due to a mechanism that is independent of elevated NE in PVAT.Funding: NIHP01HL70687, F31 HL12803501

scholarly journals Organic cation transporter 3 contributes to norepinephrine uptake into perivascular adipose tissue

2015 ◽  
Vol 309 (11) ◽  
pp. H1904-H1914 ◽  
Author(s):  
Nadia Ayala-Lopez ◽  
William F. Jackson ◽  
Robert Burnett ◽  
James N. Wilson ◽  
Janice M. Thompson ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Organic Cation ◽  
Organic Cation Transporter ◽  
Confocal Imaging ◽  
Uptake System ◽  
Sprague Dawley ◽  
Uptake Mechanism ◽  
Fluorescent Substrate ◽  
Perivascular Adipose Tissue ◽  
Organic Cation Transporter 3

Perivascular adipose tissue (PVAT) reduces vasoconstriction to norepinephrine (NE). A mechanism by which PVAT could function to reduce vascular contraction is by decreasing the amount of NE to which the vessel is exposed. PVATs from male Sprague-Dawley rats were used to test the hypothesis that PVAT has a NE uptake mechanism. NE was detected by HPLC in mesenteric PVAT and isolated adipocytes. Uptake of NE (10 μM) in mesenteric PVAT was reduced by the NE transporter (NET) inhibitor nisoxetine (1 μM, 73.68 ± 7.62%, all values reported as percentages of vehicle), the 5-hydroxytryptamine transporter (SERT) inhibitor citalopram (100 nM) with the organic cation transporter 3 (OCT3) inhibitor corticosterone (100 μM, 56.18 ± 5.21%), and the NET inhibitor desipramine (10 μM) with corticosterone (100 μM, 61.18 ± 6.82%). Aortic PVAT NE uptake was reduced by corticosterone (100 μM, 53.01 ± 10.96%). Confocal imaging of mesenteric PVAT stained with 4-[4-(dimethylamino)-styrl]- N-methylpyridinium iodide (ASP+), a fluorescent substrate of cationic transporters, detected ASP+ uptake into adipocytes. ASP+ (2 μM) uptake was reduced by citalopram (100 nM, 66.68 ± 6.43%), corticosterone (100 μM, 43.49 ± 10.17%), nisoxetine (100 nM, 84.12 ± 4.24%), citalopram with corticosterone (100 nM and 100 μM, respectively, 35.75 ± 4.21%), and desipramine with corticosterone (10 and 100 μM, respectively, 50.47 ± 5.78%). NET protein was not detected in mesenteric PVAT adipocytes. Expression of Slc22a3 (OCT3 gene) mRNA and protein in PVAT adipocytes was detected by RT-PCR and immunocytochemistry, respectively. These end points support the presence of a transporter-mediated NE uptake system within PVAT with a potential mediator being OCT3.

Abstract P142: Sex-differences In M1-like Macrophage Counts In Aortic Perivascular Adipose Tissue Precedes High Fat Diet-induced Hypertension In Dahl S Rats

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Ramya Kalyana Kumar ◽  
Hannah Garver ◽  
Erinn Liamon-Thompson ◽  
Gregory D Fink ◽  
Stephanie W Watts ◽  
...  
Keyword(s):  
T Cells ◽  
Sex Differences ◽  
Adipose Tissue ◽  
Immune Cells ◽  
Immune Cell ◽  
Memory T Cells ◽  
High Fat ◽  
Perivascular Adipose Tissue ◽  
Induced Hypertension ◽  
Hypertension Development

Perivascular adipose tissue (PVAT) may connect adiposity to hypertension because of its functions and proximity to blood vessels. Immune cells in adipose tissue are proposed to couple adiposity to hypertension development in a sex-specific fashion. It is unknown if sex-differences exist in PVAT’s immune community during the onset of adiposity-induced hypertension. Both sexes of the Dahl S rat strain become equally hypertensive (table) when fed a high fat (HFD) diet. We hypothesized that both sexes have similar immune cell composition in PVAT with the development and progression of HFD-induced hypertension. Male and female Dahl S rats were fed a regular (10% calories from fat; CD) diet or a HFD (60%) from weaning. Thoracic aorta PVAT (APVAT) was harvested at 10 (pre-hypertension), 17 (onset) or 24 (chronic) weeks (w) of diet. Macrophages (subtypes), neutrophils, mast, T (subtypes), B, NK cells were measured by flow cytometry. At 10 w, HFD females had 5X the number of M1-like macrophages vs HFD males. At 17 w, CD females had 10X the number of M2-like macrophages vs CD males. At 17 w and 24 w, males had greater number of CD4 (2X) and CD8 (1.5X) memory T cells vs females, independent of the diet (table). In summary, sex-differences in M1-like macrophage counts in APVAT precedes the development of HFD-induced hypertension in Dahl S rats. The progression of hypertension is associated with memory T cells in males and M2-like macrophages in females. This study is foundational to understand the sex-specific roles of these immune cells in regulating vascular tone in HFD-induced hypertension, underscoring the need for novel sex-specific anti-hypertensive immune modulators.

scholarly journals Restoring Perivascular Adipose Tissue Function in Obesity Using Exercise

2021 ◽  
Author(s):  
Sophie N Saxton ◽  
Lauren K Toms ◽  
Robert G Aldous ◽  
Sarah B Withers ◽  
Jacqueline Ohanian ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Contractile Function ◽  
Ex Vivo ◽  
Vascular Complications ◽  
Electrical Field Stimulation ◽  
Organic Cation Transporter ◽  
Nervous Stimulation ◽  
Perivascular Adipose Tissue ◽  
Contractile Effect ◽  
Organic Cation Transporter 3

AbstractPurposePerivascular adipose tissue (PVAT) exerts an anti-contractile effect which is vital in regulating vascular tone. This effect is mediated via sympathetic nervous stimulation of PVAT by a mechanism which involves noradrenaline uptake through organic cation transporter 3 (OCT3) and β3-adrenoceptor-mediated adiponectin release. In obesity, autonomic dysfunction occurs, which may result in a loss of PVAT function and subsequent vascular disease. Accordingly, we have investigated abnormalities in obese PVAT, and the potential for exercise in restoring function.MethodsVascular contractility to electrical field stimulation (EFS) was assessed ex vivo in the presence of pharmacological tools in ±PVAT vessels from obese and exercised obese mice. Immunohistochemistry was used to detect changes in expression of β3-adrenoceptors, OCT3 and tumour necrosis factor-α (TNFα) in PVAT.ResultsHigh fat feeding induced hypertension, hyperglycaemia, and hyperinsulinaemia, which was reversed using exercise, independent of weight loss. Obesity induced a loss of the PVAT anti-contractile effect, which could not be restored via β3-adrenoceptor activation. Moreover, adiponectin no longer exerts vasodilation. Additionally, exercise reversed PVAT dysfunction in obesity by reducing inflammation of PVAT and increasing β3-adrenoceptor and OCT3 expression, which were downregulated in obesity. Furthermore, the vasodilator effects of adiponectin were restored.ConclusionLoss of neutrally mediated PVAT anti-contractile function in obesity will contribute to the development of hypertension and type II diabetes. Exercise training will restore function and treat the vascular complications of obesity.

scholarly journals Transglutaminases Are Active in Perivascular Adipose Tissue

2021 ◽  
Vol 22 (5) ◽  
pp. 2649
Author(s):  
Alexis N. Orr ◽  
Janice M. Thompson ◽  
Janae M. Lyttle ◽  
Stephanie W. Watts
Keyword(s):  
Adipose Tissue ◽  
Vascular Remodeling ◽  
Coagulation Factor ◽  
Sprague Dawley ◽  
Rt Pcr ◽  
Ideal Model ◽  
Perivascular Adipose Tissue ◽  
Tissue Sections ◽  
Insight Into ◽  
Immunohistochemical Analyses

Transglutaminases (TGs) are crosslinking enzymes best known for their vascular remodeling in hypertension. They require calcium to form an isopeptide bond, connecting a glutamine to a protein bound lysine residue or a free amine donor such as norepinephrine (NE) or serotonin (5-HT). We discovered that perivascular adipose tissue (PVAT) contains significant amounts of these amines, making PVAT an ideal model to test interactions of amines and TGs. We hypothesized that transglutaminases are active in PVAT. Real time RT-PCR determined that Sprague Dawley rat aortic, superior mesenteric artery (SMA), and mesenteric resistance vessel (MR) PVATs express TG2 and blood coagulation Factor-XIII (FXIII) mRNA. Consistent with this, immunohistochemical analyses support that these PVATs all express TG2 and FXIII protein. The activity of TG2 and FXIII was investigated in tissue sections using substrate peptides that label active TGs when in a catalyzing calcium solution. Both TG2 and FXIII were active in rat aortic PVAT, SMAPVAT, and MRPVAT. Western blot analysis determined that the known TG inhibitor cystamine reduced incorporation of experimentally added amine donor 5-(biotinamido)pentylamine (BAP) into MRPVAT. Finally, experimentally added NE competitively inhibited incorporation of BAP into MRPVAT adipocytes. Further studies to determine the identity of amidated proteins will give insight into how these enzymes contribute to functions of PVAT and, ultimately, blood pressure.

scholarly journals The Role of Perivascular Adipose Tissue in Early Changes in Arterial Function during High-Fat Diet and Its Combination with High-Fructose Intake in Rats

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1552
Author(s):  
Jozef Torok ◽  
Anna Zemancikova ◽  
Zuzana Valaskova ◽  
Peter Balis
Keyword(s):  
Adipose Tissue ◽  
High Fat Diet ◽  
Control Diet ◽  
Sympathetic Nerves ◽  
High Fat ◽  
Perivascular Adipose Tissue ◽  
Fructose Intake ◽  
High Fructose ◽  
Wistar Kyoto ◽  
Isolated Arteries

The aim of the current study was to evaluate the influence of a high-fat diet and its combination with high-fructose intake on young normotensive rats, with focus on the modulatory effect of perivascular adipose tissue (PVAT) on the reactivity of isolated arteries. Six-week-old Wistar–Kyoto rats were treated for 8 weeks with a control diet (10% fat), a high-fat diet (HFD; 45% fat), or a combination of the HFD with a 10% solution of fructose. Contractile and relaxant responses of isolated rat arteries, with preserved and removed PVAT for selected vasoactive stimuli, were recorded isometrically by a force displacement transducer. The results demonstrated that, in young rats, eight weeks of the HFD might lead to body fat accumulation and early excitation of the cardiovascular sympathetic nervous system, as shown by increased heart rate and enhanced arterial contractile responses induced by endogenous noradrenaline released from perivascular sympathetic nerves. The addition of high-fructose intake deteriorated this state by impairment of arterial relaxation and resulted in mild elevation of systolic blood pressure; however, the increase in arterial neurogenic contractions was not detected. The diet-induced alterations in isolated arteries were observed only in the presence of PVAT, indicating that this structure is important in initiation of early vascular changes during the development of metabolic syndrome.

scholarly journals Evaluation of Anti-Obesity Activity, Acute Toxicity, and Subacute Toxicity of Probiotic Dark Tea

Biomolecules ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 99 ◽  
Author(s):  
Wang Ling ◽  
Shungeng Li ◽  
Xingcai Zhang ◽  
Yongquan Xu ◽  
Ying Gao ◽  
...  
Keyword(s):  
Body Weight ◽  
High Fat Diet ◽  
Metabolic Disorders ◽  
The Body ◽  
High Fat ◽  
Water Group ◽  
Subacute Toxicity ◽  
Infusion Group ◽  
Sd Rats ◽  
Group Ii

: Probiotic dark tea (PDT) is a novel kind of dark tea produced by fresh albino tea leaves and fermented with specific probiotics. Our study demonstrates that PDT can ameliorate high-fat diet-induced overweight and lipid metabolic disorders and shows no acute or subacute toxicity in Sprague-Dawley (SD) rats. Daily intragastric administration of 5% PDT infusion for 14 days caused no obvious effect on general physiological features and behaviors of rats. Oral administration of 1%, 2%, and 3% of PDT infusion for six weeks had no influence on the biochemistry and histopathology of rats’ organs and blood, as well as the body weight and ratios of organ/body weight. To investigate its anti-obesity activity, SD rats were randomly divided into four groups, treated with normal diet + water (Group I), high-fat diet + water (Group II), high-fat diet + 3% traditional dark tea infusion (Group III), high-fat diet + 3% PDT infusion (Group IV). After six weeks, the body weight, serum total triacylglycerol (TG) and serum total cholesterol (TC) levels of rats in Group II were significantly increased and the high-density lipoprotein cholesterol (HDL) levels were significantly decreased compared with those in the other three groups. Both traditional dark tea and PDT treatment effectively counteracted the adverse effect of a high-fat diet in SD rats. These results suggest that PDT could be applied for the prevention of obesity, which ameliorates overweight and lipid metabolic disorders and which shows no acute or subacute toxicity.

scholarly journals Maternal separation enhances anticontractile perivascular adipose tissue function in male rats on a high-fat diet

2018 ◽  
Vol 315 (6) ◽  
pp. R1085-R1095 ◽  
Author(s):  
Analia S. Loria ◽  
Frank T. Spradley ◽  
Ijeoma E. Obi ◽  
Bryan K. Becker ◽  
Carmen De Miguel ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
High Fat Diet ◽  
Life Stress ◽  
Vascular Function ◽  
Maternal Separation ◽  
Male Rats ◽  
Protective Effects ◽  
Ang Ii ◽  
High Fat ◽  
Perivascular Adipose Tissue

Clinical studies have shown that obesity negatively impacts large arteries’ function. We reported that rats exposed to maternal separation (MatSep), a model of early life stress, display enhanced angiotensin II (ANG II)-induced vasoconstriction in aortic rings cleaned of perivascular adipose tissue (PVAT) under normal diet (ND) conditions. We hypothesized that exposure to MatSep promotes a greater loss of PVAT-mediated protective effects on vascular function and loss of blood pressure (BP) rhythm in rats fed a high-fat diet (HFD) when compared with controls. MatSep was performed in male Wistar-Kyoto rats from days 2 to 14 of life. Normally reared littermates served as controls. On ND, aortic rings from MatSep rats with PVAT removed showed increased ANG II-mediated vasoconstriction versus controls; however, rings from MatSep rats with intact PVAT displayed blunted constriction. This effect was exacerbated by an HFD in both groups; however, the anticontractile effect of PVAT was greater in MatSep rats. Acetylcholine-induced relaxation was similar in MatSep and control rats fed an ND, regardless of the presence of PVAT. HFD impaired aortic relaxation in rings without PVAT from MatSep rats, whereas the presence of PVAT improved relaxation in both groups. On an HFD, immunolocalization of vascular smooth muscle-derived ANG-(1–7) and PVAT-derived adiponectin abundances were increased in MatSep. In rats fed an HFD, 24-h BP and BP rhythms were similar between groups. In summary, MatSep enhanced the ability of PVAT to blunt the heightened ANG II-induced vasoconstriction and endothelial dysfunction in rats fed an HFD. This protective effect may be mediated via the upregulation of vasoprotective factors within the adipovascular axis.

Abstract 156: Involvement of β-adrenergic System in Myocardial Dysfunction Induced by Obesity

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Ana Paula Lima-Leopoldo ◽  
Artur Ferron ◽  
Bruno Jacobsen ◽  
Dijon Campos ◽  
Renata Luvizotto ◽  
...  
Keyword(s):  
Myocardial Dysfunction ◽  
Myocardial Contraction ◽  
Experimental Models ◽  
The Body ◽  
Adrenergic System ◽  
Standard Diet ◽  
Adrenergic Stimulation ◽  
High Fat ◽  
Functional Changes ◽  
Adiposity Index

Several structural and functional changes of the heart have often been associated with human and experimental models of obesity. Some factors have been suggested as responsible for possible cardiac abnormalities in models of obesity, among them β-adrenergic system, an important mechanism of regulation of myocardial contraction and relaxation. The objetive of present study was to evaluate the . Thirty-day-old male Wistar rats were assigned to one of two groups: control (C) and obese (Ob). The C group was fed a standard diet and Ob group was fed cycles of four unsaturated high-fat diets for 15 weeks. The body fat was measured from the sum of the individual fat pad weights and the obesity was defined by adiposity index. Isolated papillary muscle preparation was performed under basal conditions and after inotropic and lusitropic maneuvers. β-adrenergic system was evaluated by using cumulative concentrations of isoproterenol and Western Blot. After 15 weeks, the Ob rats developed higher adiposity index than C rats. Obesity promoted comorbities such as glucose intolerance, insulin resistance, hyperleptinemia, and dyslipidemia; however, were not associated with changes in systolic blood pressure. The cardiac structure results post-death showed that obesity caused cardiac hypertrophy. Furthermore, Ob muscles developed similar baseline data, but myocardial responsiveness to post-rest contraction stimulus and increased extracellular Ca2+ was compromised. There were no changes in cardiac function between groups after β-adrenergic stimulation. The obesity was not accompanied by changes in protein expression of Gsα, β1 and β2 adrenergic receptors. In conclusion, the myorcardial dysfunction caused by unsaturated high-fat diet-induced obesity, after 15 weeks, is not related to β-adrenergic system impairment.

Abstract 333: Existence of Functional Norepinephrine Transport in Perivascular Adipose Tissue

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Nadia Ayala-Lopez ◽  
Robert Burnett ◽  
Janice M Thompson ◽  
Stephanie W Watts
Keyword(s):  
Blood Vessel ◽  
Contractile Function ◽  
Organic Cation Transporter ◽  
Sprague Dawley ◽  
Rt Pcr ◽  
Perivascular Adipose Tissue ◽  
Healthy State ◽  
Health And Disease ◽  
Organic Cation Transporter 3 ◽  
Beta 2 Microglobulin

Perivascular Tissue (PVAT) is a recent focus of studies for its regulation of blood vessel tone. Contraction to norepinephrine (NE) is reduced by PVAT through mechanisms not entirely clear. Loss of this anti-contractile function of PVAT occurs in obesity-related hypertension. We hypothesized that PVAT can remove NE from the blood vessel environment through transporters and reduce NE induced contraction in health. RT-PCR of mesenteric PVAT was positive for norepinephrine transporter (NET; Ct=33.2±1.4) and serotonin transporter (SERT; Ct=31.9±0.9) relative to beta-2-microglobulin. To study NE uptake in the healthy state, mesenteric and aortic PVAT from the male Sprague Dawley rat was incubated with 10 μM NE after pre-incubation with an inhibitor of transport (10 μM desipramine to inhibit NET and SERT, 100 μM corticosterone to inhibit organic cation transporter 3) or vehicle and quantified by HPLC for NE. Desipramine plus corticosterone inhibited NE uptake in mesenteric PVAT (figure) but desipramine (410.5±80.8 ng/g vs. 414.4±67.0 ng/g NE only; n=8) or corticosterone (225.0±26.1 ng/g vs. 319.2±35.9 ng/g NE only; n=5) alone did not, indicating a robust uptake capacity. In aortic PVAT, NE uptake was not inhibited by desipramine plus corticosterone (figure), desipramine (1763.5±460.8 ng/g vs. 1702.7±298.4 ng/g NE only; n=6), or corticosterone (1085.8±205.3 ng/g vs. 2245.8±506.8 ng/g NE only; n=4). Protein staining revealed bands positive for NET in mesenteric PVAT by Western blot. Taken together, we found that PVAT is a reservoir of NE that can remove NE from the blood vessel environment, an important finding to understand vasculature-PVAT interactions in health and disease.

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