A Reduction in the Amount and Anti-Contractile Effect of Periadventitial Mesenteric Adipose Tissue Precedes Hypertension Development in Spontaneously Hypertensive Rats

Gálvez-Prieto, Beatriz; Dubrovska, Galyna; Cano, Michelle; Delgado, Mercedes; Aránguez, Isabel; González, M. C.; Ruiz‐Gayo, Mariano; Gollasch, Maik; Fernández-Alfonso, Marı́a S.

doi:10.1291/hypres.31.1415

Cited by 53 publications

(49 citation statements)

References 25 publications

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“…We have previously reported diminished anticontractile effects of perivascular fat in mesenteric arteries of SHRs, 6,9 which can be explained by reduced expression of KCNQ4 channels ( Figure S5). In line, a reduced expression of vascular KCNQ4 channels contributing to increased contractility of aortas and mesenteric and renal arteries of SHRs was reported recently.…”

Section: Kcnq Channel Openers Improve the Diminished Anticontractile mentioning

confidence: 87%

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Role of KCNQ Channels in Skeletal Muscle Arteries and Periadventitial Vascular Dysfunction

et al. 2013

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KCNQ channels have been identified in arterial smooth muscle. However, their role in vasoregulation and chronic vascular diseases remains elusive. We tested the hypothesis that KCNQ channels contribute to periadventitial vasoregulation in peripheral skeletal muscle arteries by perivascular adipose tissue and that they represent novel targets to rescue periadventitial vascular dysfunction. Two models, spontaneously hypertensive rats and New Zealand obese mice, were studied using quantitative polymerase chain reaction, the patch-clamp technique, membrane potential measurements, myography of isolated vessels, and blood pressure telemetry. In rat Gracilis muscle arteries, anticontractile effects of perivascular fat were inhibited by the KCNQ channel blockers XE991 and linopirdine but not by other selective K + channel inhibitors. Accordingly, XE991 and linopirdine blocked noninactivating K + currents in freshly isolated Gracilis artery smooth muscle cells. mRNAs of several KCNQ channel subtypes were detected in those arteries, with KCNQ4 channels being dominant. In spontaneously hypertensive rats, the anticontractile effect of perivascular fat in Gracilis muscle arteries was largely reduced compared with Wistar rats. However, the vasodilator effects of KCNQ channel openers and mRNA expression of KCNQ channels were normal. Furthermore, KCNQ channel openers restored the diminished anticontractile effects of perivascular fat in spontaneously hypertensive rats. Moreover, KCNQ channel openers reduced arterial blood pressure in both models of hypertension independent of ganglionic blockade. Thus, our data suggest that KCNQ channels play a pivotal role in periadventitial vasoregulation of peripheral skeletal muscle arteries, and KCNQ channel opening may be an effective mechanism to improve impaired periadventitial vasoregulation and associated hypertension.

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Section: Kcnq Channel Openers Improve the Diminished Anticontractile mentioning

confidence: 87%

“…There is defective periadventitial regulation of arterial tone in SHRs, 6,9 angiotensin II infusion-treated hypertensive rats, 14 and NZO mice. 10,11 Similar disturbances have been reported in subcutaneous circulation of humans.…”

Section: Discussionmentioning

confidence: 98%

Role of KCNQ Channels in Skeletal Muscle Arteries and Periadventitial Vascular Dysfunction

et al. 2013

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“…[18][19][20][21][22] In contrast, spontaneously hypertensive rats had reduced amounts of PVAT in resistance arteries with impaired anti-contractile function. 23 These studies provide compelling evidence that PVAT plays an important role in the regulation of vascular tone. We used high-fat-fed C57Bl/6 male mice, which are a well-established model for diet-induced obesity, to test the hypothesis that alterations in PVAT play a role in the pathogenesis of endothelial dysfunction in obesity.…”

Section: Editorial P 1300mentioning

confidence: 96%

Periadventitial Adipose Tissue Promotes Endothelial Dysfunction via Oxidative Stress in Diet-Induced Obese C57Bl/6 Mice

Ketonen

Shi

Martonen

et al. 2010

Circ J

186

168

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Background: Biological substances derived from perivascular fat modulate vascular tone, thus alterations in periadventitial adipose tissue (PVAT) may aggravate endothelial dysfunction in obesity. Methods and Results:Male C57Bl/6 mice were fed either a high-fat diet or standard laboratory chow for 8 months. Vascular responses were studied in organ bath chambers from abdominal aortic ring preparations in the absence or presence of PVAT. The amount of PVAT as well as the cross-sectional area of adipocytes were increased in obese mice. In the presence of PVAT, obese aortas displayed impaired endothelium-dependent vasodilation whereas endothelium-independent vasodilatation was unaltered. Endothelium-dependent vasodilatation was restored after removal of PVAT and after reducing superoxide and hydrogen peroxide formation in the vascular wall by Tiron or polyethylene-glycol-catalase, respectively. PVAT from obese mice showed increased formation of hydrogen peroxide and superoxide. The PVAT-derived oxidative stress was abolished by pretreatment with the reduced nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase inhibitor, apocynin. The anti-contractile function of PVAT found in lean mice was completely abolished in obese mice, but partially restored after pretreatment with Tiron. The mRNA expressions of monocyte chemotactic protein-1, leptin and NADPH oxidase were markedly higher in the PVAT of obese than lean mice. Conclusions:PVAT promotes endothelial dysfunction in diet-induced obese C57Bl/6 mice via mechanisms that are linked to increased NADPH oxidase-derived oxidative stress and increased production of pro-inflammatory cytokines. (Circ J 2010; 74: 1479 - 1487

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“…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. …”

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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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A Reduction in the Amount and Anti-Contractile Effect of Periadventitial Mesenteric Adipose Tissue Precedes Hypertension Development in Spontaneously Hypertensive Rats

Cited by 53 publications

References 25 publications

Role of KCNQ Channels in Skeletal Muscle Arteries and Periadventitial Vascular Dysfunction

Role of KCNQ Channels in Skeletal Muscle Arteries and Periadventitial Vascular Dysfunction

Periadventitial Adipose Tissue Promotes Endothelial Dysfunction via Oxidative Stress in Diet-Induced Obese C57Bl/6 Mice

Perivascular Adipose Tissue, Potassium Channels, and Vascular Dysfunction

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