Epigallocatechin gallate attenuates ET-1-induced contraction in carotid artery from type 2 diabetic OLETF rat at chronic stage of disease

Ando

et al. 2017

Purinergic Signalling

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Uridine 5′-diphosphate (UDP) plays an important role in controlling vascular tone; however, UDP-mediated response in metabolic syndromes, including obesity and type 2 diabetes in females, remains unclear. In this study, we investigated UDP-mediated response in the aorta of female obese Otsuka Long-Evans Tokushima Fatty (OLETF) rats and control Long-Evans Tokushima Otsuka (LETO) rats. In OLETF rat aortas precontracted by phenylephrine (PE) (vs. LETO), (1) UDP-induced relaxation was increased, whereas acetylcholine (ACh)-induced relaxation was decreased; (2) no UDP-or ACh-induced relaxations were observed in endothelial denudation, whereas UDP-induced small contraction was observed; and (3) N G -nitro-L-arginine [L-NNA, a nitric oxide (NO) synthase inhibitor] eliminated UDP-induced relaxation and small contraction, whereas caused contrasting responses by ACh, including slight relaxations (LETO) and contractions (OLETF). Indomethacin, a cyclooxygenase inhibitor, eliminated the difference in UDP-and ACh-induced relaxations between the groups by increased UDP-induced relaxation in the LETO group and increased ACh-induced relaxation in the OLETF group. MRS2578, a P2Y 6 receptor antagonist, eliminated the difference in UDP-induced relaxations between the groups by decreasing UDP-induced relaxation in the OLETF group. MRS2578 had no effect on UDP-induced contraction in endothelium-denuded aortas. Therefore, these findings demonstrate opposite trends of relaxations by UDP and ACh in OLETF and LETO rat aortas. These differences may be attributed to the imbalance between NO and vasoconstrictor prostanoids upon stimulations. Increased UDP-induced relaxation in OLETF rat aorta may be caused by the activation of endothelial MRS2578-sensitive P2Y 6 receptor.

Section: Introductionmentioning

confidence: 73%

UDP-induced relaxation is enhanced in aorta from female obese Otsuka Long–Evans Tokushima Fatty rats

Kobayashi

Ando

et al. 2017

Purinergic Signalling

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“…[41][42][43][44] For the relaxation studies, renal and carotid arterial rings were precontracted with a submaximal concentration of PE (i.e., 1-3 µM). When the PE-induced contraction had reached a plateau, ACh (10 −9 -10 −5 M), ANP (10 −10 -10 −7 M), or SNP (10 −10 -10…”

Section: )mentioning

confidence: 99%

“…42,43) We also performed experiments to construct a concentration-response curve for NS1619 (a BK Ca activator, 10…”

Section: )mentioning

confidence: 99%

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Relaxation Induced by Atrial Natriuretic Peptide Is Impaired in Carotid but Not Renal Arteries from Spontaneously Hypertensive Rats Due to Reduced BK<sub>Ca</sub> Channel Activity

Biological & Pharmaceutical Bulletin

Watanabe

Yamada

et al. 2015

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Atrial natriuretic peptide (ANP) plays an important role in vascular functions such as blood pressure regulation and relaxant activity. Individual vascular beds exhibit differences in vascular reactivity to various ligands, however, the difference in responsiveness to ANP between carotid and renal arteries and the molecular mechanisms of its vasorelaxant activity in a pathophysiological state, including hypertension, remain unclear. We therefore investigated this issue by exposing carotid and renal artery rings obtained from spontaneously hypertensive rats (SHR) to ANP. In the SHR artery (vs. control WKY artery), the ANP-induced relaxations were reduced in carotid artery but not renal artery. Acetylcholine-induced relaxations were reduced in both arteries in SHR (vs. WKY). Sodium nitroprusside-induced relaxation was similar in both arteries between the groups. In carotid arteries, the ANP-induced relaxation was not affected by endothelial denudation or by treatment with inhibitors of nitric oxide synthase, cyclooxygenase, the voltage-dependent potassium channel, or ATP-sensitive potassium channel in arteries from both SHR and WKY. In the carotid artery from WKY but not SHR, the ANP-induced relaxation was significantly reduced by inhibition of the large-conductance calcium-activated potassium channel (BK Ca ). The BK Ca activator-induced relaxation was reduced in the SHR artery (vs. WKY). These results suggest that ANP-induced relaxation is impaired in the carotid artery from SHR and this impairment may be at least in part due to the reduction of BK Ca activity rather than endothelial components.Key words atrial natriuretic peptide (ANP); carotid artery; potassium channel; relaxation; spontaneously hypertensive rat (SHR) Hypertension contributes markedly to global cardiovascular morbidity and mortality.1-3) Vascular dysfunction is a hallmark of hypertension and frequently leads to the development of atherosclerosis, stroke, and peripheral arterial disease.1,4) In vascular dysfunction, abnormalities of vascular smooth muscle cells and endothelial cells are key factors in the development of hypertension-associated vascular complications. 5-7)It has been shown that endogenous vasoactive peptides such as angiotensin II, endothelin-1, urotensin II, and natriuretic peptides play an important role in the regulation of vascular tone in (patho) physiological conditions. 8-11) Several reports suggested that the signalings of vasoactive peptides, including their production, metabolism, and affected vascular functions, are altered in arteries from hypertensive patients and animal models.6,10,12) Therefore, the manipulation of vasoactive peptide signaling is one of the most important strategies against the development of vascular dysfunction in hypertension.Atrial natriuretic peptide (ANP) has received particular attention since its effects on the cardiac function and blood pressure regulation have been reported through various mechanisms, including diuretic, natriuretic, and vasorelaxation. [13][14][15][16][17][18][19][20][2...

“…17) Indeed, we have also shown that long-term chlorogenic acid (CA) treatment (2 months) can normalize the impaired endothelium-dependent relaxation seen in diabetic rats. 18) Although these effects of polyphenol treatment could be secondary to its protective effect against oxidant stress, there is preliminary evidence indicating that polyphenols themselves may contribute to regulation of the vascular tone. 19) When administered in vitro, resveratrol (RV) enhances endothelial vasorelaxation by potentiating NO synthase and increasing the phosphorylation of Akt and endothelial nitric oxide synthase (eNOS), suggesting that RV alone has a vasodilatory effect.…”

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confidence: 99%

Effect of Short-term Polyphenol Treatment on Endothelial Dysfunction and Thromboxane A<sub>2</sub> Levels in Streptozotocin-Induced Diabetic Mice

Taguchi

Hida

Biological & Pharmaceutical Bulletin

et al. 2014

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Diabetes is characterized by the development of endothelial dysfunction, which affects both nitric oxide (NO)-mediated relaxation and endothelium-derived contracting factors, associated with vascular oxidative stress. There is a growing body of evidence suggesting that polyphenols have several beneficial effects, such as antioxidant and anti-inflammatory activities. This study investigated whether short-term treatment with polyphenols (chlorogenic acid (CA), morin (MO), resveratrol (RV)) can improve endothelial dysfunction related to diabetes. Aorta reactivity was determined in organ chambers, and we measured NO production and thromboxane B 2 (TXB 2 ; a metabolite of TXA 2 ) from aortas in response to acetylcholine (ACh). Streptozotocin (