Abnormalities of endothelium-dependent responses in mesenteric arteries from Otsuka Long-Evans Tokushima Fatty (OLETF) rats are improved by chronic treatment with thromboxane A2 synthase inhibitor

Matsumoto, Takayuki; Takaoka, Eri; Ishida, Keiko; Nakayama, Naoaki; Noguchi, Eri; Kobayashi, Tsuneo; Kamata, Katsuo

doi:10.1016/j.atherosclerosis.2008.11.015

Cited by 22 publications

(11 citation statements)

References 24 publications

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“…The concentrations of nitrite (NO 2 Ϫ ) and nitrate (NO 3 Ϫ ) in the effluent from each tissue were measured using the method described previously (40). To evaluate the release of NO metabolites in mesenteric arteries, each mesenteric ring was placed in KHS at 37°C and then treated with IRL1620 (3 ϫ 10 Ϫ8 M) for 5 min.…”

Section: Reagentsmentioning

confidence: 99%

Involvement of NO and MEK/ERK pathway in enhancement of endothelin-1-induced mesenteric artery contraction in later-stage type 2 diabetic Goto-Kakizaki rat

Matsumoto¹,

Ishida²,

Nakayama³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

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Endothelin (ET)-1 is a likely candidate for a key role in diabetic vascular complications. However, no abnormalities in the vascular responsiveness to ET-1 have been identified in the chronic stage of type 2 diabetes. Our goal was to look for abnormalities in the roles played by ET receptors (ET(A) and ET(B)) in the mesenteric artery of the type 2 diabetic Goto-Kakizaki (GK) rat and to identify the molecular mechanisms involved. Using mesenteric arteries from later-stage (32-38 wk old) individuals, we compared the ET-1-induced contraction and the relaxation induced by the selective ET(B) receptor agonist IRL1620 between GK rats and control Wistar rats. Mesenteric artery ERK activity and the protein expressions for ET receptors and MEK were also measured. In GK rats (vs. age-matched Wistar rats), we found as follows. 1) The ET-1-induced contraction was greater and was attenuated by BQ-123 (ET(A) antagonist) but not by BQ-788 (ET(B) antagonist). In the controls, BQ-788 augmented this contraction. 2) Both the relaxation and nitric oxide (NO) production induced by IRL1620 were reduced. 3) ET-1-induced contraction was enhanced by N(G)-nitro-l-arginine (l-NNA; NO synthase inhibitor) but suppressed by sodium nitroprusside (NO donor). 4) The enhanced ET-1-induced contraction was reduced by MEK/ERK pathway inhibitors (PD-98059 or U0126). 5) ET-1-stimulated ERK activation was increased, as were the ET(A) and MEK1/2 protein expressions. 6) Mesenteric ET-1 content was increased. These results suggest that upregulation of ET(A), a defect in ET(B)-mediated NO signaling, and activation of the MEK/ERK pathway together represent a likely mechanism mediating the hyperreactivity to ET-1 examined in this study.

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Section: Reagentsmentioning

confidence: 99%

Involvement of NO and MEK/ERK pathway in enhancement of endothelin-1-induced mesenteric artery contraction in later-stage type 2 diabetic Goto-Kakizaki rat

Matsumoto¹,

Ishida²,

Nakayama³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

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“…Each frozen sample was homogenized as described previously [2], [5], [6], [8], [23], [24] or stated above. Blots were performed as reported [2], [5], [6], [8], [23], [24].…”

Section: Methodsmentioning

confidence: 99%

“…Blots were performed as reported [2], [5], [6], [8], [23], [24]. To investigate the expressions of phospho-eNOS and phospho-Akt in such arteries upon ACh stimulation, carotid arterial rings from a given rat were incubated with KHS at 37°C and then exposed to 10 −6 M ACh or vehicle (water) for 15 min.…”

Section: Methodsmentioning

confidence: 99%

“…Indeed, it has been well established that the pathogenesis and progression of vascular complications of diabetes are characterized by the development of endothelial dysfunction, which correlates with a decrease in vasodilator factor release, such as nitric oxide (NO) or prostacyclin, as well as an increase in vasoconstrictor production, such as Thromboxane A 2 (TXA 2 ) [1], [5]–[8]. NO generated from endothelial NO synthase (eNOS) plays a key role in vascular homeostasis.…”

Section: Introductionmentioning

confidence: 99%

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Activated Platelets from Diabetic Rats Cause Endothelial Dysfunction by Decreasing Akt/Endothelial NO Synthase Signaling Pathway

et al. 2014

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Diabetes is associated with endothelial dysfunction and platelet activation, both of which may contribute to increased cardiovascular risk. The purpose of this study was to characterize circulating platelets in diabetes and clarify their effects on endothelial function. Male Wistar rats were injected with streptozotocin (STZ) to induce diabetes. Each experiment was performed by incubating carotid arterial rings with platelets (1.65×107 cells/mL; 30 min) isolated from STZ or control rats. Thereafter, the vascular function was characterized in isolated carotid arterial rings in organ bath chambers, and each expression and activation of enzymes involved in nitric oxide and oxidative stress levels were analyzed. Endothelium-dependent relaxation induced by acetylcholine was significantly attenuated in carotid arteries treated with platelets isolated from STZ rats. Similarly, treatment with platelets isolated from STZ rats significantly reduced ACh-induced Akt/endothelial NO synthase signaling/NO production and enhanced TXB2 (metabolite of TXA2), while CD61 (platelet marker) and CD62P (activated platelet marker) were increased in carotid arteries treated with platelets isolated from STZ rats. Furthermore, the platelets isolated from STZ rats decreased total eNOS protein and eNOS dimerization, and increased oxidative stress. These data provide direct evidence that circulating platelets isolated from diabetic rats cause dysfunction of the endothelium by decreasing NO production (via Akt/endothelial NO synthase signaling pathway) and increasing TXA2. Moreover, activated platelets disrupt the carotid artery by increasing oxidative stress.

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“…Treatment of type 2 diabetic OLETF rats with a TxS inhibitor suppressed ACh‐induced TxA 2 production, partly improved ACh‐induced endothelium‐dependent, NO‐dependent and EDHF‐dependent relaxations, and inhibited ACh‐induced endothelium‐dependent contractions in superior mesenteric arteries. These data suggest that TxS inhibition normalizes endothelial dysfunction in type 2 diabetes (Matsumoto et al ., ).…”

Section: Prostanoids: Endothelium‐derived Contracting Factorsmentioning

confidence: 99%

Constrictor prostanoids and uridine adenosine tetraphosphate: vascular mediators and therapeutic targets in hypertension and diabetes

Matsumoto

Goulopoulou

Taguchi

et al. 2015

British J Pharmacology

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Vascular dysfunction plays a pivotal role in the development of systemic complications associated with arterial hypertension and diabetes. The endothelium, or more specifically, various factors derived from endothelial cells tightly regulate vascular function, including vascular tone. In physiological conditions, there is a balance between endothelium-derived factors, that is, relaxing factors (endothelium-derived relaxing factors; EDRFs) and contracting factors (endothelium-derived contracting factors; EDCFs), which mediate vascular homeostasis. However, in disease states, such as diabetes and arterial hypertension, there is an imbalance between EDRF and EDCF, with a reduction of EDRF signalling and an increase of EDCF signalling. Among EDCFs, COX-derived vasoconstrictor prostanoids play an important role in the development of vascular dysfunction associated with hypertension and diabetes. Moreover, uridine adenosine tetraphosphate (Up4A), identified as an EDCF in 2005, also modulates vascular function. However, the role of Up4A in hypertension-and diabetes-associated vascular dysfunction is unclear. In the present review, we focused on experimental and clinical evidence that implicate these two EDCFs (vasoconstrictor prostanoids and Up4A) in vascular dysfunction associated with hypertension and diabetes. Abbreviations AA, arachidonic acid; AICAR, 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside; AMPK, AMP-activated protein kinase; CDK2, cyclin-dependent kinase 2; cPLA2, cytosolic PLA2; DOCA, deoxycorticosterone-acetate; E2, 17β-oestradiol; ECs, endothelial cells; EDCF, endothelium-derived contracting factor; EDHF, endothelium-derived hyperpolarizing factor; EDRF, endothelium-derived relaxing factor; EPA, eicosapentaenoic acid; ER, endoplasmic reticulum; ET-1, endothelin-1; GK, Goto-Kakizaki; GPER, G protein-coupled oestrogen receptor; HETEs, hydroxyeicosatetraenoic acid; HO-1, haem oxygenase-1; HUVEC, human umbilical vein endothelial cells; L-NAME, N G -nitro-l-arginine methyl ester; L-PGDS, lipocalin-type PGD synthase; MLC20, myosin light chain 20; NO, nitric oxide; NSAIDs, non-steroidal anti-inflammatory drugs; OLETF, Otsuka Long-Evans Tokushima Fatty; OPN, osteopontin; PDGFR, platelet-derived growth factor receptor; PGI2, prostacyclin; PGIS, prostacyclin synthase; ROCK, Rho kinase; ROS, reactive oxygen species; S6K, S6 kinase; SHR, spontaneously hypertensive rats; SMCs, smooth muscle cells; STZ, streptozotocin; TP, TxA2/endoperoxide receptor; TxA2, thromboxane A2; TxS, thromboxane synthase; Up4A, uridine adenosine tetraphosphate; VP, vasopressin; WKY, Wistar-Kyoto ratsThe endothelium plays a pivotal role in the regulation of vascular tone (Vapaatalo and Mervaala, 2001;Pries and Kuebler, 2006;Flammer and Luscher, 2010;Toda et al., 2010;Flammer et al., 2012; Favero et al., 2014). In response to mechanical forces (e.g. shear stress) and endogenous ligands, endothelial cells (ECs) release a diversity of factors that mediate or directly induce vascular smooth muscle contraction or relaxation (Vapaatalo and Me...

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Abnormalities of endothelium-dependent responses in mesenteric arteries from Otsuka Long-Evans Tokushima Fatty (OLETF) rats are improved by chronic treatment with thromboxane A2 synthase inhibitor

Cited by 22 publications

References 24 publications

Involvement of NO and MEK/ERK pathway in enhancement of endothelin-1-induced mesenteric artery contraction in later-stage type 2 diabetic Goto-Kakizaki rat

Involvement of NO and MEK/ERK pathway in enhancement of endothelin-1-induced mesenteric artery contraction in later-stage type 2 diabetic Goto-Kakizaki rat

Activated Platelets from Diabetic Rats Cause Endothelial Dysfunction by Decreasing Akt/Endothelial NO Synthase Signaling Pathway

Constrictor prostanoids and uridine adenosine tetraphosphate: vascular mediators and therapeutic targets in hypertension and diabetes

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