Anticontractile Effect of Perivascular Adipose Tissue and Leptin are Reduced in Hypertension

Gálvez-Prieto, Beatriz; Somoza, Beatriz; Gil‐Ortega, Marta; García‐Prieto, Concha F.; Heras, Ana Isabel de las; González, M. C.; Arribas, Silvia M.; Aránguez, Isabel; Bolbrinker, Juliane; Kreutz, Reinhold; Ruiz‐Gayo, Mariano; Fernández-Alfonso, Marı́a S.

doi:10.3389/fphar.2012.00103

Cited by 87 publications

(75 citation statements)

References 51 publications

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“…30 Similarly to adiponectin, leptin has also been proposed as a candidate for PVRF in a hypertension mouse model. 31 Leptin, however, is perhaps not ADRF in the systemic circulation because the PVAT of Zucker fa/fa rats that lack the leptin receptor still display anticontractile properties. 3 As mentioned above, angiotensin-1 to 7 and methyl palmitate are also proposed as PVRF.…”

Section: Pvrf: Potential Candidatesmentioning

confidence: 99%

Perivascular Adipose Tissue, Potassium Channels, and Vascular Dysfunction

Tano

Schleifenbaum

Gollasch

2014

ATVB

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Abstract-Perivascular adipose tissue has been recognized unequivocally as a major player in the pathology of metabolic and cardiovascular diseases. Through its production of adipokines and the release of other thus far unidentified factors, this recently discovered adipose tissue modulates vascular regulation and the myogenic response. After the discovery of its ability to diminish the vessel's response to vasoconstrictors, a new paradigm established adipose-derived relaxing factor (ADRF) as a paracrine smooth muscle cells' potassium channel opener that could potentially help combat vascular dysfunction. This review will discuss the role of ADRF in vascular dysfunction in obesity and hypertension, the different potassium channels that can be activated by this factor, and describes new pharmacological tools that can mimic the ADRF effect and thus can be beneficial against vascular dysfunction in cardiovascular disease. [19][20][21][22] and are also observable on veins. 23 The release of ADRF from PVAT is strongly dependent on the concentration of Ca 2+ and seems to be dependent on the activation of intracellular pathways involving tyrosine kinase and protein kinase A. In contrast, perivascular nerve endings, notably presynaptic neuronal N-type Ca 2+ , Na + channels, calcitonin gene-related peptide, cannabinoid, and vanilloid receptors, do not play an important role in this process.4 Importantly, recent experiments have shown a dual role of PVAT in the initiation and progression of obesity. In effect, PVAT (similarly to endothelium) in animal and human models of hypertension, obesity, and metabolic syndrome becomes dysfunctional and loses its anticontractile properties, likely because of a decrease in PVRF release. 16,[24][25][26][27] It is, therefore, of utmost importance to determine the nature of PVRFs as well as its targets for the paracrine regulation of PVAT. PVRF: Potential CandidatesSeveral studies have tried to pinpoint the nature of PVRFs. The role of adiponectin as PVRF has been thus far inconclusive. Vessels from the aorta and mesenteric arteries of adiponectin-knockout mice have been initially shown to maintain their anticontractile properties. 16 In contrast, recent studies in mesenteric vessels of wild-type mice advance that the vasorelaxing and hyperpolarizing effects of adiponectin rely on the opening of maxi Ca 2+ -activated K + (BK Ca ) channels. 28,29 In addition, a factor that might be adiponectin is released after stimulation of rat and murine mesenteric arteries with β3 adrenoreceptor. This latter factor seems to exert its paracrine effect by activation of AMPK and opening of BK ca channels. 30 Similarly to adiponectin, leptin has also been proposed as a candidate for PVRF in a hypertension mouse model. 31 Leptin, however, is perhaps not ADRF in the systemic circulation because the PVAT of Zucker fa/fa rats that lack the leptin receptor still display anticontractile properties. 3 As mentioned above, angiotensin-1 to 7 and methyl palmitate are also proposed as PVRF. A study using aortas from...

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Section: Pvrf: Potential Candidatesmentioning

confidence: 99%

Perivascular Adipose Tissue, Potassium Channels, and Vascular Dysfunction

Tano

Schleifenbaum

Gollasch

2014

ATVB

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“…[23][24][25][26] Patients after bariatric surgery displayed improved insulin sensitivity, reduced blood pressure, and a restored anticontractile effect of PVAT. 2 Interestingly, BAT surrounding the aorta has been reported to be resistant to obesity-induced inflammation, suggesting that BAT may help to protect the vasculature during pathological conditions.…”

Section: Discussionmentioning

confidence: 99%

“…19,20 In pathologies such as obesity and hypertension, WAT is characterized by low-grade inflammation and is associated with insulin resistance and vascular dysfunction. 21,22 These changes are also evident in PVAT, where the anticontractile effect is lost, [23][24][25][26][27][28][29][30] resulting in a procontractile phenotype. 23 We previously demonstrated, in experimental models of obesity-related type 2 diabetes mellitus, that PVAT-derived factors induce endothelial dysfunction and regulate vascular contractility and remodeling.…”

Section: Arterioscler Thromb Vasc Biolmentioning

confidence: 99%

Brown Adipose Tissue Regulates Small Artery Function Through NADPH Oxidase 4–Derived Hydrogen Peroxide and Redox-Sensitive Protein Kinase G-1α

Friederich‐Persson

Cat

Persson

et al. 2017

ATVB

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Objective— Biomedical interest in brown adipose tissue (BAT) has increased since the discovery of functionally active BAT in adult humans. Although white adipose tissue (WAT) influences vascular function, vascular effects of BAT are elusive. Thus, we investigated the regulatory role and putative vasoprotective effects of BAT, focusing on hydrogen peroxide, nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4), and redox-sensitive signaling. Approach and Results— Vascular reactivity was assessed in wild-type and Nox4-knockout mice (Nox4 −/− ) by wire myography in the absence and presence of perivascular adipose tissue of different phenotypes from various adipose depots: (1) mixed WAT/BAT (inguinal adipose tissue) and (2) WAT (epididymal visceral fat) and BAT (intrascapular fat). In wild-type mice, epididymal visceral fat and perivascular adipose tissue increased EC 50 to noradrenaline without affecting maximum contraction. BAT increased EC 50 and significantly decreased maximum contraction, which were prevented by a hydrogen peroxide scavenger (polyethylene glycated catalase) and a specific cyclic GMP–dependent protein kinase G type-1α inhibitor (DT-3), but not by inhibition of endothelial nitric oxide synthase or guanylate cyclase. BAT induced dimerization of cyclic GMP–dependent protein kinase G type-1α and reduced phosphorylation of myosin light chain phosphatase subunit 1 and myosin light chain 20. BAT from Nox4-knockout mice displayed reduced hydrogen peroxide levels and no anticontractile effects. Perivascular adipose tissue from β 3 agonist–treated mice displayed browned perivascular adipose tissue and an increased anticontractile effect. Conclusions— We identify a novel vasoprotective action of BAT through an anticontractile effect that is mechanistically different to WAT. Specifically, BAT, via Nox4-derived hydrogen peroxide, induces cyclic GMP–dependent protein kinase G type-1α activation, resulting in reduced vascular contractility. BAT may constitute an interesting therapeutic target to restore vascular function and prevent vascular complications in cardiovascular diseases.

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“…Several studies [23,28,31,38,39,42,45,46,47,48] have examined the effect of hypertension on the anticontractile effect of PVAT. The general agreement in all these studies is that the anticontractile effect of PVAT is attenuated in artery segments from hypertensive rats irrespective of the experimental model used.…”

Section: Effect Of Hypertension On the Anticontractile Effect Of Pvatmentioning

confidence: 99%

“…An increased release of contracting factors cannot be ruled out. The reduced anticontractile effect of PVAT in established hypertension has been shown to be associated with a reduced release of vasodilators, leptin [28,47] and methyl palmitate [39], from the PVAT. However, the observation that the direct dilator effect of leptin on angiotensin II-induced vasoconstriction was attenuated in artery segments from SHR [49] would indicate that whatever mechanism mediates leptin-induced vascular smooth muscle relaxation is also impaired in vessels from SHR.…”

Section: Effect Of Hypertension On the Anticontractile Effect Of Pvatmentioning

confidence: 99%

Perivascular Adipose Tissue, Vascular Reactivity and Hypertension

Oriowo

2014

Med Princ Pract

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Most blood vessels are surrounded by a variable amount of adventitial adipose tissue, perivascular adipose tissue (PVAT), which was originally thought to provide mechanical support for the vessel. It is now known that PVAT secretes a number of bioactive substances including vascular endothelial growth factor, tumor necrosis factor-alpha (TNF-α), leptin, adiponectin, insulin-like growth factor, interleukin-6, plasminogen activator substance, resistin and angiotensinogen. Several studies have shown that PVAT significantly modulated vascular smooth muscle contractions induced by a variety of agonists and electrical stimulation by releasing adipocyte-derived relaxing (ADRF) and contracting factors. The identity of ADRF is not yet known. However, several vasodilators have been suggested including adiponectin, angiotensin 1-7, hydrogen sulfide and methyl palmitate. The anticontractile effect of PVAT is mediated through the activation of potassium channels since it is abrogated by inhibiting potassium channels. Hypertension is characterized by a reduction in the size and amount of PVAT and this is associated with the attenuated anticontractile effect of PVAT in hypertension. However, since a reduction in size and amount of PVAT and the attenuated anticontractile effect of PVAT were already evident in prehypertensive rats with no evidence of impaired release of ADRF, there is the possibility that the anticontractile effect of PVAT was not directly related to an altered function of the adipocytes per se. Hypertension is characterized by low-grade inflammation and infiltration of macrophages. One of the adipokines secreted by macrophages is TNF-α. It has been shown that exogenously administered TNF-α enhanced agonist-induced contraction of a variety of vascular smooth muscle preparations and reduced endothelium-dependent relaxation. Other procontractile factors released by the PVAT include angiotensin II and superoxide. It is therefore possible that the loss could be due to an increased amount of these proinflammatory and procontractile factors. More studies are definitely required to confirm this.

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Anticontractile Effect of Perivascular Adipose Tissue and Leptin are Reduced in Hypertension

Cited by 87 publications

References 51 publications

Perivascular Adipose Tissue, Potassium Channels, and Vascular Dysfunction

Perivascular Adipose Tissue, Potassium Channels, and Vascular Dysfunction

Brown Adipose Tissue Regulates Small Artery Function Through NADPH Oxidase 4–Derived Hydrogen Peroxide and Redox-Sensitive Protein Kinase G-1α

Perivascular Adipose Tissue, Vascular Reactivity and Hypertension

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