Autonomic nerves and perivascular fat: Interactive mechanisms

Bulloch, J.M.; Daly, C.J.

doi:10.1016/j.pharmthera.2014.02.005

Cited by 47 publications

(47 citation statements)

References 156 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the present study, we discuss NE uptake in PVAT with the consideration that most NE that the blood vessel is exposed to is not circulating NE but rather NE released from sympathetic nerve boutons in and around the blood vessel. Autonomic nervous system interactions with PVAT and its effects on the blood vessel have been recognized (12). NE released from the nerves that innervate PVAT and the vascular smooth muscle cell could be taken up by PVAT, thus reducing vascular contraction.…”

Section: Discussionmentioning

confidence: 99%

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

Ayala‐Lopez

Jackson

Burnett

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Watts SW. Organic cation transporter 3 contributes to norepinephrine uptake into perivascular adipose tissue. Am J Physiol Heart Circ Physiol 309: H1904 -H1914, 2015. First published October 2, 2015; doi:10.1152/ajpheart.00308.2015.-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 M) in mesenteric PVAT was reduced by the NE transporter (NET) inhibitor nisoxetine (1 M, 73.68 Ϯ 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 M, 56.18 Ϯ 5.21%), and the NET inhibitor desipramine (10 M) with corticosterone (100 M, 61.18 Ϯ 6.82%). Aortic PVAT NE uptake was reduced by corticosterone (100 M, 53.01 Ϯ 10.96%). Confocal imaging of mesenteric PVAT stained with 4-[4-(dimethylamino)-styrl]-N-methylpyridinium iodide (ASP ϩ ), a fluorescent substrate of cationic transporters, detected ASP ϩ uptake into adipocytes. ASP ϩ (2 M) uptake was reduced by citalopram (100 nM, 66.68 Ϯ 6.43%), corticosterone (100 M, 43.49 Ϯ 10.17%), nisoxetine (100 nM, 84.12 Ϯ 4.24%), citalopram with corticosterone (100 nM and 100 M, respectively, 35.75 Ϯ 4.21%), and desipramine with corticosterone (10 and 100 M, respectively, 50.47 Ϯ 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. PERIVASCULAR ADIPOSE TISSUE (PVAT) closely envelops many blood vessels of the body (65). This relationship between PVAT and the blood vessel has earned PVAT its place as the fourth layer of the blood vessel, the "tunica adiposa" (14). Beyond providing structural support, PVAT has many roles in modulating blood vessel function (68). The release of vasoactive molecules from PVAT influences vascular function by altering the proliferation, migration, inflammation, and contraction of vascular smooth muscle (9, 20 -22, 24, 46, 68, 72). Interestingly, a releasable pool of catecholamines is present in PVAT (5, 67). Although both contractile and anticontractile substances can be released from PVAT (9,22,24,25,72), the presence of PVAT on blood vessels generally reduces vessel contraction in response to various agonists, including norepinephrine (NE) (64). Knowledge on how these mechanisms interact to influence the anticontractile properties of PVAT in NE-induced contraction is not complete (36).The anticontractile effect of PVAT is lost in obesity and hypertension, implicating PVAT as an integral lin...

show abstract

Section: Discussionmentioning

confidence: 99%

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

Ayala‐Lopez

Jackson

Burnett

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…Different stressors trigger the HPA-axis, SNS/SAM or other neuroendocrine axes with varied intensity [3,88,89] and stimuli of different intensity differentially regulate nerve activity leading to the preferential release of neurotransmitters and/or neuropeptides [90]. Acute social defeat activates the sympathetic nerves innervating the BAT with a magnitude comparable to acute cold exposure [85].…”

Section: The Dichotomous Effect Of Stress On Obesity: An Energy Balanmentioning

confidence: 99%

The Dichotomous Effect of Chronic Stress on Obesity

Razzoli

Bartolomucci

2016

Trends in Endocrinology & Metabolism

View full text Add to dashboard Cite

Obesity and metabolic diseases are linked to chronic stress and low socio-economic status. The mechanistic link between stress and obesity has not been clarified, partly due to the inherent complexity exemplified by the bidirectional effect of stress on eating and body weight. Recent studies focusing on adaptive-thermogenesis and brown adipose tissue (BAT) function support a dichotomous relationship to explain the impact of stress on obesity: stress promotes obesity in the presence of hyperphagia and unchanged BAT function; stress results in weight-loss/obesity-resistance in the presence of hypophagia, or when hyperphagia is associated with BAT recruitment and enhanced thermogenesis. Mechanistically dissecting the bidirectional effects of stress on metabolic outcomes might open new avenues for innovative pharmacotherapies for the treatment of obesity-associated diseases.

show abstract

“…Sympathetic varicosities are found in the adventitial-medial border of the blood vessel, and this means that the nerves must carry through the PVAT itself. These nerves are likely exposed to substances in PVAT such as chemerin (5). We tested the hypothesis that chemerin potentiates the actions of sympathetic nerves in isolated vasculature.…”

Section: This Research Is Noteworthy In That It Supports a New Mechamentioning

confidence: 99%

The adipokine chemerin amplifies electrical field-stimulated contraction in the isolated rat superior mesenteric artery

Darios

Winner

Charvat

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Darios ES, Winner BM, Charvat T, Krasinksi A, Punna S, Watts SW. The adipokine chemerin amplifies electrical field-stimulated contraction in the isolated rat superior mesenteric artery. Am J Physiol Heart Circ Physiol 311: H498 -H507, 2016. First published July 1, 2016; doi:10.1152/ajpheart.00998.2015.-The adipokine chemerin causes arterial contraction and is implicated in blood pressure regulation, especially in obese subjects with elevated levels of circulating chemerin. Because chemerin is expressed in the perivascular adipose tissue (PVAT) that surrounds the sympathetic innervation of the blood vessel, we tested the hypothesis that chemerin (endogenous and exogenous) amplifies the sympathetic nervous system in mediating electrical field-stimulated (EFS) contraction. The superior mesenteric artery, with or without PVAT and with endothelium and sympathetic nerve intact, was mounted into isolated tissue baths and used for isometric contraction and stimulation. Immunohistochemistry validated a robust expression of chemerin in the PVAT surrounding the superior mesenteric artery. EFS (0.3-20 Hz) caused a frequency-dependent contraction in isolated arteries that was reduced by the chemerin receptor ChemR23 antagonist CCX832 alone (100 nM; with, but not without, PVAT), but not by the inactive congener CCX826 (100 nM). Exogenous chemerin-9 (1 M)-amplified EFSinduced contraction in arteries (with and without PVAT) was blocked by CCX832 and the ␣-adrenergic receptor antagonist prazosin. CCX832 did not directly inhibit, nor did chemerin directly amplify, norepinephrine-induced contraction. Whole mount immunohistochemical experiments support colocalization of ChemR23 with the sympathetic nerve marker tyrosine hydroxylase in superior mesenteric PVAT and, to a lesser extent, in arteries and veins. These studies support the idea that exogenous chemerin modifies sympathetic nervemediated contraction through ChemR23 and that ChemR23 may be endogenously activated. This is significant because of the wellappreciated role of the sympathetic nervous system in blood pressure control. BECAUSE OF ITS LOCATION, the perivascular adipose tissue (PVAT) has the potential to affect the function of the blood vessels it encases. This can occur by secretion of adipokines that directly affect vascular tone, such as the relaxant adiponectin (25). We recently discovered the protein chemerin in PVAT and demonstrated that a shorter chemerin agonist, chemerin-9, caused direct arterial contraction through activation of the best-characterized chemerin receptor, ChemR23 (3,8,27,33,38,48). Chemerin is secreted from the liver and fat depots (10), functioning as an adipokine that regulates adipogenesis (12,31,32) and as an activator of inflammatory cells (13,50,52). Circulating levels of chemerin are positively associated with body mass index (1,4,9,16,36,37,40). Because of our long-term interest in understanding whether chemerin could play a role in obesity-associated hypertension, we turned our attention to a means by which arterial function could be m...

show abstract

Autonomic nerves and perivascular fat: Interactive mechanisms

Cited by 47 publications

References 156 publications

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

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

The Dichotomous Effect of Chronic Stress on Obesity

The adipokine chemerin amplifies electrical field-stimulated contraction in the isolated rat superior mesenteric artery

Contact Info

Product

Resources

About