Hydrogen sulfide derived from periadventitial adipose tissue is a vasodilator

Fang, Liping; Zhao, Jing; Chen, Yu; Ma, Tao; Gao, Xu; Tang, Chaoshu; Liu, Xinmin; Geng, Bin

doi:10.1097/hjh.0b013e328330a900

Cited by 134 publications

(130 citation statements)

References 29 publications

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“…38 One of the best candidates described thus far for PVRF/ADRF is the cystathionine-γ-lyase-derived H 2 S, although it exhibits differential effects in the mouse and the rat. In effect, our group 39,40 and Fang et al 41 have demonstrated that inhibitors of cystathionine-γ-lyase significantly reduced the anticontractile effect of PVAT in rat aortic rings, whereas murine mesenteric arteries and aorta were not affected. 40 Interestingly, vasoconstrictors as well as the statin atorvastatin seem to increase the release of H 2 S from the PVAT in rats, thus increasing its anticontractile effect.…”

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confidence: 72%

“…40 Interestingly, vasoconstrictors as well as the statin atorvastatin seem to increase the release of H 2 S from the PVAT in rats, thus increasing its anticontractile effect. 41,42 Importantly, NaHS, a H 2 S donor, can cause a dose-dependent relaxation that is inhibited by treatment with the KCNQ (K v 7) channel blocker XE991. 40 The cystathionine-γ-lyase inhibitor β-cyano-l-alanine had no effect on coronary flow, which might be explained by organ differences or low-dose β-cyano-l-alanine used in this study.…”

Section: Pvrf: Potential Candidatesmentioning

confidence: 99%

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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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confidence: 72%

Section: Pvrf: Potential Candidatesmentioning

confidence: 99%

Perivascular Adipose Tissue, Potassium Channels, and Vascular Dysfunction

Tano

Schleifenbaum

Gollasch

2014

ATVB

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“…17 Recent data indicate that H 2 S represents a candidate or modulator of ADRF. 15,16 H 2 S activates K v channels encoded by KCNQ genes, at least in visceral arteries such as rat aorta and mouse mesenteric arteries. 16 In the present study, we used rat Gracilis muscle arteries to study periadventitial vasoregulation in peripheral skeletal muscle arteries.…”

Section: Discussionmentioning

confidence: 99%

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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“…CSE is not expressed in rat endothelial cells; however, H 2 S is synthesized in these cells in a 3-MST-dependent manner (Shibuya et al, 2009). H 2 S is also produced by perivascular adipose tissue (Fang et al, 2009). Moreover, H 2 S, especially at low concentrations, may trigger some vasoconstrictor mechanisms, such as direct inhibition of endothelial NO synthase or inactivation of NO by binding it to form inactive nitrosothiol (Ali et al, 2006).…”

Section: Role Of H 2 S In the Regulation Of Vascular Tone And Blood Pmentioning

confidence: 99%

Hypoxia in the Renal Medulla: Implications for Hydrogen Sulfide Signaling

Bełtowski

2010

J Pharmacol Exp Ther

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Hydrogen sulfide (H 2 S) is enzymatically generated in mammalian tissues from either L-cysteine or L-homocysteine. H 2 S possesses multiple biological activities, including regulation of vascular tone and blood pressure. Hydrogen sulfide produced in endothelial cells, vascular smooth muscle cells, and perivascular adipose tissue dilates blood vessels by activating ATP-sensitive potassium channels. In addition, H 2 S produced locally within the kidney stimulates natriuresis and diuresis by increasing glomerular filtration and inhibiting tubular sodium reabsorption. Because H 2 S is oxidized in mitochondria in pO 2 -dependent manner and ambient pO 2 is physiologically low in the renal medulla, it is expected that the activity of H 2 S is higher in the medullary region than the cortical region. H 2 S, accumulating in increased amounts in the renal medulla under hypoxic conditions, may function as an oxygen sensor that restores O 2 balance by increasing medullary blood flow, reducing energy requirements for tubular transport, and directly inhibiting mitochondrial respiration. Hypoxia is an important pathogenic factor in many renal diseases, such as ischemia/reperfusion-or nephrotoxin-induced acute renal failure, progression of chronic nephropathies, diabetic nephropathy, and arterial hypertension. Deficiency of endogenous H 2 S may contribute to the pathogenesis of these pathologies by compromising medullary oxygenation, and administration of H 2 S donors may be of therapeutic value in these disorders.Studies performed during the last decade indicate that, apart from NO and CO, H 2 S is the third "gasotransmitter" involved in the regulation of various physiological functions, including vascular tone and blood pressure, inflammatory reaction, neurotransmission and gastrointestinal system function. H 2 S is enzymatically synthesized in three metabolic pathways (Fig. 1): 1) desulfhydration of L-cysteine or L-homocysteine by cystathionine ␥-lyase (CSE, EC 4.4.1.1), 2) desulfhydration of L-cysteine by cystathionine ␤-synthase (CBS, EC 4.2.1.22), and 3) transamination of L-cysteine by cysteine aminotransferase (identical with aspartate aminotransferase) to 3-mercaptopyruvate, followed by its desulfhydration to pyruvate by 3-mercaptopyruvate sulfurtransferase (3-MST, EC 2.8.1.2). Hydrogen sulfide activates ATP-sensitive potassium channels (K ATP ) in various cells, although many other signaling mechanisms have also been described. H 2 S is inactivated by binding to hemoglobin to form sulfhemoglobin, excretion in exhaled air, and, first and foremost, oxidation in mitochondria. Many studies addressed the role of H 2 S in the regulation of vascular tone and blood pressure. Indeed, it is suggested that H 2 S deficiency may contribute to the pathogenesis of arterial hypertension both in experimental animal models and in humans. Recently, renal synthesis and activity of H 2 S have been characterized (Xia et al., 2009). Because renal sodium handling has a prominent role in the long-term regulation of blood pressure (apart...

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Hydrogen sulfide derived from periadventitial adipose tissue is a vasodilator

Abstract: These results suggested PAT could endogenously generate H(2)S, which might act as an adipocyte-derived relaxing factor and contribute to the pathogenesis of hypertension.

Cited by 134 publications

References 29 publications

Perivascular Adipose Tissue, Potassium Channels, and Vascular Dysfunction

Perivascular Adipose Tissue, Potassium Channels, and Vascular Dysfunction

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

Hypoxia in the Renal Medulla: Implications for Hydrogen Sulfide Signaling

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