Abstract P627: The β3 Adrenergic Receptor is Partially Responsible for Anti-contractile Effect of Perivascular Adipose Tissue in Rat Mesenteric Resistance Arteries

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Theodora Szasz ◽  
Takayuki Matsumoto ◽  
Camilla F Wenceslau ◽  
R Clinton Webb
Keyword(s):  
Adipose Tissue ◽  
Adrenergic Receptor ◽  
Metabolic Diseases ◽  
Mesenteric Arteries ◽  
Resistance Arteries ◽  
Perivascular Adipose Tissue ◽  
Contractile Responses ◽  
Contractile Effect ◽  
Brown Adipose ◽  
Male Wistar Rats

In normal conditions, perivascular adipose tissue (PVAT) decreases contractile responses non-specifically in various vascular beds. This anti-contractile effect of PVAT is reduced in metabolic diseases and hypertension. The β3 adrenergic receptor (β3AR) is a G protein-coupled receptor expressed in adipocytes and involved in lipolysis and thermoregulation. We have previously demonstrated that chronic systemic infusion with a β3AR agonist induces white-to-brown adipose tissue remodeling and enhanced anti-contractile effects of PVAT via activation of cystathionine gamma lyase, enzyme involved in hydrogen sulfide synthesis. We hypothesized that the β3AR is directly mediating release of PVAT relaxing factors. Endothelium-intact mesenteric resistance arteries from adult male Wistar rats were used to measure contractile responses in the presence and absence of PVAT. In the absence of PVAT, the β3AR agonist CL316243 (1 nM-10 μM) did not directly induce relaxation of U46619-contracted arteries. In control conditions, norepinephrine (NE)-induced contraction was significantly reduced in the presence of PVAT. In contrast, incubation with the selective β3AR antagonist L-748337 (100 nM) led to a significant increase in NE-induced contraction in PVAT-intact arteries, while no change was observed in the absence of PVAT (figure). These data suggest that β3AR mediates the anti-contractile effect of PVAT on NE-induced contraction in resistance mesenteric arteries. Considering the structural and functional alterations of PVAT in hypertension, future studies may reveal a potential novel therapeutic approach via targeting of the PVAT β3AR pathway.

scholarly journals Effect of Perivascular Adipose Tissue on Arterial Adrenergic Contractions in Normotensive and Hypertensive Rats With High Fructose Intake

2017 ◽  
pp. S537-S544
Author(s):  
A. ZEMANČÍKOVÁ ◽  
J. TÖRÖK
Keyword(s):  
Adipose Tissue ◽  
Mesenteric Arteries ◽  
Heart Weight ◽  
Inhibitory Influence ◽  
Moderate Increase ◽  
Hypertensive Rats ◽  
Perivascular Adipose Tissue ◽  
Contractile Responses ◽  
Fructose Intake ◽  
High Fructose

The aim of this study was to investigate the effect of high fructose intake associated with moderate increase in adiposity on rat arterial adrenergic responses and their modulation by perivascular adipose tissue (PVAT). After eight-week-lasting substitution of drinking water with 10 % fructose solution in adult normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR), their systolic blood pressure, plasma triglycerides, and relative liver weight were elevated when compared to their respective control groups. Moreover, in SHR, body weight and relative heart weight were increased after treatment with fructose. In superior mesenteric arteries, PVAT exerted inhibitory influence on adrenergic contractile responses and this effect was markedly stronger in control WKY than in SHR. In fructose-administered WKY, arterial adrenergic contractions were substantially reduced in comparison with the control group; this was caused mainly by enhancement of anticontractile action of PVAT. The diminution of the mesenteric arterial contractions was not observed after fructose treatment in SHR. We conclude that the increase in body adiposity due to fructose overfeeding in rats might have pro-hypertensive effect. However, in WKY it might cause PVAT-dependent and independent reduction in arterial contractile responses to adrenergic stimuli, which could attenuate the pathological elevation in vascular tone.

Abstract 138: Altered Vascular Reactivity in Mice Overexpressing Adipocyte Mineralocorticoid Receptors - Role of Rho Kinase.

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Aurelie Nguyen Dinh Cat ◽  
Tayze T Antunes ◽  
Glaucia E Callera ◽  
Augusto C Montezano ◽  
Ying He ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Vascular Function ◽  
Vascular Reactivity ◽  
Molecular Mechanisms ◽  
Rho Kinase ◽  
Mesenteric Arteries ◽  
Mineralocorticoid Receptors ◽  
Resistance Arteries ◽  
Brown Adipose

Aldosterone (aldo) plays a role in cardiovascular diseases, including hypertension and obesity. We previously demonstrated that adipocyte-derived factors regulate vascular function and cell signaling in cultured vascular smooth muscle cells. Moreover, adipocytes are able to produce aldo, which influences vascular reactivity. Plasma levels of aldo are positively correlated with obesity and hypertension. However, the pathophysiological role of aldo and mineralocorticoid receptors (MR) in adipose tissue and its interactions with the vasculature remains elusive. In our study, we investigated molecular mechanisms whereby activation of MR, in adipocytes, leads to release of vascular reactive factors and regulation of vascular tone, using a conditional transgenic mouse model that overexpresses MR only in the adipocytes. Vascular reactivity of resistance mesenteric arteries to acetylcholine (Ach), sodium nitroprusside and phenylephrine (Phe), in the absence or presence of fat conditioned medium (Fcm) from control and adipocyte overexpressing MR (DT) mice, was performed by myography. In basal conditions, endothelial dysfunction was not observed in DT or control mice. However, in the presence of Fcm from DT mice, relaxation to Ach was impaired in control mice (Ach 10 -6 M: 77.5±9.6% no Fcm vs. 49.8±7.5% Fcm, p<0.05), an effect blocked by N-acetyl-cysteine (anti-oxidant) (Ach 10 -6 M: 82.2±6.6%). Resistance arteries from DT mice had decreased Phe-induced contraction, compared to control mice (Phe 10 -5 M: 2.7±0.2 mN/mm CT vs. 1.7±0.2 mN/mm DT, p<0.05). Phosphorylation of ezrin, a marker of Rho kinase activation, measured by immunoblotting, was decreased in white and brown adipose tissues of DT (CT: 3.1±0.7 vs. DT: 0.6±0.1, arbitrary units, p<0.05). In conclusion, MR in adipocytes may play an important role in the regulation of vascular function, and may be involved in vascular oxidative stress. MR in adipocytes is also important to the anti-contractile properties of the adipose tissue through downregulation of Rho kinase signaling. Our study identiy novel mechanisms linking vascular and adipose biology through adipocyte MRs.

Alteration of perivascular adipose tissue function in angiotensin II-induced hypertension

2009 ◽  
Vol 87 (11) ◽  
pp. 944-953 ◽  
Author(s):  
Robert M.K.W. Lee ◽  
Lili Ding ◽  
Chao Lu ◽  
Li-Ying Su ◽  
Yu-Jing Gao
Keyword(s):  
Blood Pressure ◽  
Adipose Tissue ◽  
Angiotensin Ii ◽  
Vascular Function ◽  
Wistar Rats ◽  
Mesenteric Arteries ◽  
Resistance Arteries ◽  
Hypertensive Rats ◽  
Perivascular Adipose Tissue ◽  
And Control

We studied the role of perivascular adipose tissue (PVAT) in the control of vascular function in an in vivo experimental model of hypertension produced by angiotensin II infusion by osmotic minipump in adult male Wistar rats. Two weeks after infusion with angiotensin II, blood pressure in treated rats was significantly elevated but heart rate was reduced compared with control rats infused with physiological saline. Contraction of aorta from the 2 groups of rats in response to phenylephrine or serotonin was significantly attenuated by the presence of PVAT in both the presence and absence of endothelium. This attenuation effect on contraction to phenylephrine was higher, however, in vessels from control rats than in vessels from hypertensive rats in the absence of endothelium. In the mesenteric resistance arteries, lumen diameter was larger in both hypertensive and control vessels with intact PVAT than in vessels with PVAT removed. The medial wall was thicker in arteries from hypertensive rats. The presence of PVAT potentiated the contraction induced by KCl in mesenteric arteries from control rats, but not in hypertensive rats. PVAT also attenuated the contraction of mesenteric arteries in response to phenylephrine or serotonin in both hypertensive and control groups. Mesenteric arteries from hypertensive rats were more responsive to stimulation by serotonin than those from control rats. We conclude that the increased blood pressure of Wistar rats that occurred after infusion with angiotensin II was associated with changes in the functions of PVAT in the aorta and mesenteric arteries and in the structure and function of resistance arteries.

scholarly journals Perivascular adipose tissue-derived adiponectin activates BKCa channels to induce anticontractile responses

2013 ◽  
Vol 304 (6) ◽  
pp. H786-H795 ◽  
Author(s):  
Fiona M. Lynch ◽  
Sarah B. Withers ◽  
Zhihong Yao ◽  
Matthias E. Werner ◽  
Gill Edwards ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Knockout Mice ◽  
Wild Type Mouse ◽  
Mesenteric Arteries ◽  
Wild Type ◽  
Bkca Channels ◽  
Perivascular Adipose Tissue ◽  
Contractile Responses ◽  
Small Arteries ◽  
Oxide Synthase

This study aims to identify the potential mechanisms by which perivascular adipose tissue (PVAT) reduces tone in small arteries. Small mesenteric arteries from wild-type and large-conductance Ca2+-activated K+ (BKCa) channel knockout mice were mounted on a wire myograph in the presence and absence of PVAT, and contractile responses to norepinephrine were assessed. Electrophysiology studies were performed in isolated vessels to measure changes in membrane potential produced by adiponectin. Contractile responses from wild-type mouse small arteries were significantly reduced in the presence of PVAT. This was not observed in the presence of a BKCa channel inhibitor or with nitric oxide synthase (NOS) inhibition or in BKCa or adiponectin knockout mice. Solution transfer experiments demonstrated the presence of an anticontractile factor released from PVAT. Adiponectin-induced vasorelaxation and hyperpolarization in wild-type arteries were not evident in the absence of or after inhibition of BKCa channels. PVAT from BKCa or adiponectin knockout mice failed to elicit an anticontractile response in wild-type arteries. PVAT releases adiponectin, which is an anticontractile factor. Its effect on vascular tone is mediated by activation of BKCa channels on vascular smooth muscle cells and adipocytes and by endothelial mechanisms.

scholarly journals Influence of Age on Anticontractile Effect of Perivascular Adipose Tissue in Normotensive and Hypertensive Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Anna Zemančíková ◽  
Jozef Török
Keyword(s):  
Adipose Tissue ◽  
Vascular Dysfunction ◽  
Age Groups ◽  
Isometric Tension ◽  
Mesenteric Arteries ◽  
Hypertensive Rats ◽  
Perivascular Adipose Tissue ◽  
Contractile Responses ◽  
Wky Rats ◽  
Wistar Kyoto

Perivascular adipose tissue (PVAT) and its vasomodulatory effects play an important role in the physiology and pathophysiology of blood vessels. Alterations in PVAT associated with reduction in its anticontractile influence are proven to contribute to vascular dysfunction in hypertension. The aim of this study was to examine whether the changes in PVAT properties could participate in progression of vascular abnormalities in developing spontaneously hypertensive rats (SHR). Normotensive Wistar-Kyoto (WKY) rats and SHR, both in 5th and in 12th week of age, were used. Systolic blood pressure was similar between WKY rats and SHR in 5th week of age; however, in 12th week, it was significantly increased in SHR comparing to WKY rats. The amount of retroperitoneal fat was higher in WKY rats in both age groups, whereas body weight was higher in WKY rats only in 12th week, when compared to age-matched SHR. From isolated superior mesenteric arteries, two ring preparations were prepared for isometric tension recording, one with PVAT intact and other with PVAT removed. In WKY rats as well as in SHR, arterial contractile responses to noradrenaline, applied cumulatively on rings, were significantly inhibited in the presence of intact PVAT. In both age groups, anticontractile effect of PVAT was higher in WKY rats than in SHR. Neurogenic contractions, induced by electrical stimulation of perivascular sympathoadrenergic nerves, were significantly attenuated in the presence of PVAT in WKY mesenteric arteries from both age groups; however, in arteries from SHR, intact PVAT had no influence on this type of contractile responses. The results suggest that in SHR impairment of anticontractile effect of PVAT precedes hypertension and might contribute to its development.

scholarly journals The Inhibition of Ureteral Motility by Periureteral Adipose Tissue

ISRN Urology ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-7
Author(s):  
Lyndsey M. Killian ◽  
Stuart J. Bund
Keyword(s):  
Nitric Oxide ◽  
Adipose Tissue ◽  
Smooth Muscle ◽  
Nitric Oxide Synthase Inhibitor ◽  
Perivascular Adipose Tissue ◽  
Contractile Responses ◽  
Tissue Removal ◽  
Male Wistar Rats ◽  
Synthase Inhibitor ◽  
Oxide Synthase

Perivascular adipose tissue exerts an anticontractile influence on vascular smooth muscle. This study was conducted to determine whether periureteral adipose tissue (PUAT) could exert a similar influence upon ureteral smooth muscle. Acetylcholine-stimulated (10−7 M–10−4 M) contractile responses of ureteral segments obtained from male Wistar rats were recorded in the presence and absence of PUAT. Ureters with PUAT generated phasic contractile responses with significantly lower frequencies () and magnitudes () compared with ureters cleared of their periureteral adipose tissue. Removal of PUAT significantly increased the frequency () and magnitude () of the contractile responses. Bioassay experiments demonstrated that ureters with PUAT released a transferable factor that significantly reduced frequencies (), but not magnitudes, of the contractile responses of ureters cleared of PUAT. The nitric oxide synthase inhibitor L-NNA (10−4 M) did not significantly influence the anticontractile effect exerted by ureters with PUAT. This is the first study to demonstrate that ureteral motility is influenced by its surrounding adipose tissue. The PUAT has an anticontractile effect which is mediated by a transferable factor released from the PUAT. The identity of the factor is unknown but does not exert its effect through nitric oxide.

scholarly journals A Differential Pattern of Batokine Expression in Perivascular Adipose Tissue Depots From Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Alberto Mestres-Arenas ◽  
Joan Villarroya ◽  
Marta Giralt ◽  
Francesc Villarroya ◽  
Marion Peyrou
Keyword(s):  
Adipose Tissue ◽  
Growth Factor ◽  
Thoracic Aorta ◽  
Abdominal Aorta ◽  
Vascular Function ◽  
Vascular System ◽  
Mesenteric Arteries ◽  
Fibroblast Growth Factor 21 ◽  
Perivascular Adipose Tissue ◽  
Brown Adipose

Depending on its anatomical placement, perivascular adipose tissue (PVAT) has been found to possess features more (e.g., aortic thoracic) or less (e.g., aortic abdominal) similar to brown/beige adipose tissue in mice, whereas PVAT surrounding the mesenteric arteries and the caudal part of abdominal aorta is similar to white fat. PVAT is thought to influence vascular function through the effects of adipose-secreted molecules on vessels. Brown adipose tissue was recently shown to play differential secretory role via secretion of the so-called batokines but the involvement of differential batokine production in PVAT brown/beige plasticity was unclear. The current study characterizes for the first time the expression of batokines at aortic thoracic PVAT (tPVAT) and aortic abdominal PVAT (aPVAT) in comparison with typical brown and white adipose depots, in basal and thermogenically activated conditions. We found that both PVAT depots increased their expression of genes encoding the batokines bone morphogenetic protein-8b (BMP8B), fibroblast growth factor-21 (FGF21), and kininogen-2 (KNG2) in response to cold, indicating that, under cold-induced thermogenic activation, both thoracic aorta and abdominal aorta would experience intense local exposure to these PVAT-secreted batokines. In contrast, the gene expression levels of growth/differentiation factor-15 and vascular endothelial growth factor-A were induced only in tPVAT. Under short-term high-fat diet-induced thermogenic activation, the thoracic aorta would be specifically exposed to a local increase in PVAT-originating BMP8B, FGF21, and KNG2. Our data support the notion that acquisition of a brown/beige phenotype in PVAT is associated with upregulation of batokines, mainly BMP8B, FGF21, and KNG2, that can differentially target the vascular system.

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 DsbA-L deficiency in T cells promotes diet-induced thermogenesis through suppressing IFN-γ production

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Haiyan Zhou ◽  
Xinyi Peng ◽  
Jie Hu ◽  
Liwen Wang ◽  
Hairong Luo ◽  
...  
Keyword(s):  
T Cells ◽  
Adipose Tissue ◽  
T Cell ◽  
Energy Homeostasis ◽  
Metabolic Diseases ◽  
Therapeutic Potential ◽  
Whole Body ◽  
Brown Adipose ◽  
Ifn Γ ◽  
Diet Induced Thermogenesis

AbstractAdipose tissue-resident T cells have been recognized as a critical regulator of thermogenesis and energy expenditure, yet the underlying mechanisms remain unclear. Here, we show that high-fat diet (HFD) feeding greatly suppresses the expression of disulfide-bond A oxidoreductase-like protein (DsbA-L), a mitochondria-localized chaperone protein, in adipose-resident T cells, which correlates with reduced T cell mitochondrial function. T cell-specific knockout of DsbA-L enhances diet-induced thermogenesis in brown adipose tissue (BAT) and protects mice from HFD-induced obesity, hepatosteatosis, and insulin resistance. Mechanistically, DsbA-L deficiency in T cells reduces IFN-γ production and activates protein kinase A by reducing phosphodiesterase-4D expression, leading to increased BAT thermogenesis. Taken together, our study uncovers a mechanism by which T cells communicate with brown adipocytes to regulate BAT thermogenesis and whole-body energy homeostasis. Our findings highlight a therapeutic potential of targeting T cells for the treatment of over nutrition-induced obesity and its associated metabolic diseases.

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