Perivascular Adipose Tissue-Enhanced Vasodilation in Metabolic Syndrome Rats by Apelin and N-Acetyl–l-Cysteine-Sensitive Factor(s)

Kagota, Satomi; Maruyama‐Fumoto, Kana; Iwata, Saki; Shimari, Miho; Koyanagi, Shiori; Shiokawa, Yayoi; McGuire, John J.; Shinozuka, Kazumasa

doi:10.3390/ijms20010106

Cited by 16 publications

(29 citation statements)

References 48 publications

(69 reference statements)

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“…PVAT has been recognized to regulate vascular tone via releasing important adipokines. Apelin is one of these important adipokines (Kagota et al 2019). Kagota and collegues reported that the vasorelaxant effect level of apelin was higher in the presence of PVAT.…”

Section: Discussionmentioning

confidence: 99%

[Pyr1]apelin-13 relaxes the rat thoracic aorta via APJ, NO, AMPK, and potassium channels

Şahintürk¹,

Demirel²,

Özyener³

et al. 2021

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In this study, the effect and effect mechanisms of [Pyr1]apelin-13, the dominant apelin isoform in the human cardiovascular tissues and human plasma, on vascular contractility were investigated. The vascular rings obtained from the thoracic aortas of the male Wistar Albino rats were placed in the isolated tissue bath system. After the equilibration period, [Pyr1]apelin-13 (10 −9 to 10 −6 M) was applied cumulatively to the aortic rings pre-contracted with phenylephrine in the plateau phase. The protocol was repeated in the presence of specific signaling pathway inhibitors (F13A, L-NAME, dorsomorphin, TEA, U0126, or indomethacin) to determine the effect mechanisms of [Pyr1]apelin-13. [Pyr1]apelin-13 induced a dose-dependent relaxation in the pre-contracted aortic rings. APJ, eNOS, AMPK, and potassium channel inhibition statistically significantly decreased the vasodilator effect of [Pyr1]apelin-13. MAPK and COX inhibition didn't statistically significantly changed the vasodilator effect of [Pyr1]apelin-13. In conclusion, [Pyr1]apelin-13 relaxes the rat thoracic aorta via APJ, NO, AMPK, and potassium channels.

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Section: Discussionmentioning

confidence: 99%

[Pyr1]apelin-13 relaxes the rat thoracic aorta via APJ, NO, AMPK, and potassium channels

Şahintürk¹,

Demirel²,

Özyener³

et al. 2021

gpb

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“…The treatment started at 13 weeks of age ( T 0 ) and continued for 10 consecutive weeks. The age range of animals was chosen based on the studies showing that the “breakdown” of the PVAT compensatory system occurs at 23 weeks of age, 16,17 while the specific doses of tofogliflozin were previously used in Zucker diabetic rats and db/db mice. 6 Rats were provided a standard chow diet (CE-2; Clea Japan Inc., Tokyo, Japan) and water ad libitum during the experimental period.…”

Section: Methodsmentioning

confidence: 99%

“…We have previously shown that the PVAT around the mesenteric arteries compensates for the effects of impaired nitric oxide (NO)-dependent vasodilation on the circulatory system, a condition that develops when these rats reach 17 and 20 weeks of age, but this compensatory function disappears as MetS progresses (around 23 and 30 weeks of age). 16,17 We have also reported that aged SHRSP.ZF rats exhibit ventricular diastolic dysfunction 18,19 and investigated the potential mechanisms underlying the deterioration of PVAT compensatory function associated with the development of cardiac dysfunction in MetS. We also reported that angiotensin II type I receptor antagonists (ARBs), including azilsartan, telmisartan, and olmesartan, protect against MetS-associated vascular and cardiac dysfunction in SHRSP.ZF rats.…”

Section: Introductionmentioning

confidence: 99%

A Sodium Glucose Cotransporter 2 Inhibitor Fails to Improve Perivascular Adipose Tissue-Mediated Modulation of Vasodilation and Cardiac Function in Rats With Metabolic Syndrome

Kagota

Maruyama‐Fumoto

McGuire

et al. 2021

J Cardiovasc Pharmacol Ther

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Arterial perivascular adipose tissue (PVAT) can elicit vasodilator signals complementary to those elicited by the endothelium in SHRSP.Z- Leprfa/IzmDmcr (SHRSP.ZF) rats, an animal model of metabolic syndrome (MetS). Here, we tested whether a glucose cotransporter 2 inhibitor (SGLT2-i; tofogliflozin) increased this PVAT effect to prevent the deterioration of cardiac function in aging SHRSP.ZF rats. Tofogliflozin treatments (1 or 10 mg/kg/day) or vehicle (control) were administered for 10 weeks by oral gavage to SHRSP.ZF rats, starting at 13 weeks of age. At 23 weeks of age, glucose levels in the serum and urine (24 h after the last administration) were determined using commercial kits. Vasodilator responsiveness of PVAT-surrounded or PVAT-free superior mesenteric arteries was determined using acetylcholine with organ-bath methods. Cardiac ventricular function and coronary flow were determined using Langendorff heart preparations. Serum and urine glucose levels in SGLT2-i treatment groups did not differ from those in the controls, but the ratios of glycated to non-glycated albumin were lower than those in the controls. Tofogliflozin treatments did not alter relaxations in the presence of PVAT or affect relaxations of PVAT-free arteries. Left ventricular systolic pressures, maximum rate of pressure decline, and coronary flow in ex vivo hearts did not differ among the treatment groups. PVAT effects and cardiac dysfunction were not altered by tofogliflozin treatment in SHRSP.ZF rats with MetS. These results do not provide strong evidence to support the use of SGLT2-i as a cardiovascular protective therapy in MetS, which occurs prior to the onset of type 2 diabetes.

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“…In rats, aging reportedly attenuated the anti-contractile effect of PVAT around the thoracic aorta, while reducing the amount of brown adipose tissue-like PVAT ( 59 ). In the mesenteric arteries of SHRSP.Z-Leprfa/IzmDmcr rats (SHRSP.ZF) with metabolic syndrome, vascular dysfunction is compensated by a PVAT-dependent mechanism, which disappears with age ( 60 ). Compared with young C57BL/6JRj mice, middle-aged mice showed more PVAT hypertrophy ( 61 ); furthermore, the mean single adipocyte area in PVAT was significantly increased, while the expression level of protein inhibitor of activated signal transducer and activators of transcription 1 (a key negative regulator of inflammation) was decreased.…”

Section: Roles Of Pvat In Vascular Diseasementioning

confidence: 99%

Role of Inflammation in Vascular Disease-Related Perivascular Adipose Tissue Dysfunction

et al. 2021

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Perivascular adipose tissue (PVAT) is the connective tissue around most blood vessels throughout the body. It provides mechanical support and maintains vascular homeostasis in a paracrine/endocrine manner. Under physiological conditions, PVAT has anti-inflammatory effects, improves free fatty acid metabolism, and regulates vasodilation. In pathological conditions, PVAT is dysfunctional, secretes many anti-vasodilator factors, and participates in vascular inflammation through various cells and mediators; thus, it causes dysfunction involving vascular smooth muscle cells and endothelial cells. Inflammation is an important pathophysiological event in many vascular diseases, such as vascular aging, atherosclerosis, and hypertension. Therefore, the pro-inflammatory crosstalk between PVAT and blood vessels may comprise a novel therapeutic target for the prevention and treatment of vascular diseases. In this review, we summarize findings concerning PVAT function and inflammation in different pathophysiological backgrounds, focusing on the secretory functions of PVAT and the crosstalk between PVAT and vascular inflammation in terms of vascular aging, atherosclerosis, hypertension, diabetes mellitus, and other diseases. We also discuss anti-inflammatory treatment for potential vascular diseases involving PVAT.

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Perivascular Adipose Tissue-Enhanced Vasodilation in Metabolic Syndrome Rats by Apelin and N-Acetyl–l-Cysteine-Sensitive Factor(s)

Cited by 16 publications

References 48 publications

[Pyr1]apelin-13 relaxes the rat thoracic aorta via APJ, NO, AMPK, and potassium channels

[Pyr1]apelin-13 relaxes the rat thoracic aorta via APJ, NO, AMPK, and potassium channels

A Sodium Glucose Cotransporter 2 Inhibitor Fails to Improve Perivascular Adipose Tissue-Mediated Modulation of Vasodilation and Cardiac Function in Rats With Metabolic Syndrome

Role of Inflammation in Vascular Disease-Related Perivascular Adipose Tissue Dysfunction

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