Two Types of Overcontraction Are Involved in Intrarenal Artery Dysfunction in Type II Diabetic Mouse

Nobe, Koji; Takenouchi, Yasuhiro; Kasono, Keizo; Hashimoto, Terumasa; Honda, Kazuo

doi:10.1124/jpet.114.216747

Cited by 8 publications

(7 citation statements)

References 30 publications

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“…3b ). Phenylephrine, an α-adrenergic receptor agonist, stimulates Ca 2+ entry through voltage-gated and store-operated Ca 2+ channels [ 28 ], and activates Ca 2+ -sensitization pathways such as protein kinase C (PKC) and Rho-kinase [ 29 , 30 ]. NO reduces Ca 2+ entry into vascular smooth muscle [ 31 ] and c-GMP-dependent protein kinase causes phosphorylation and inactivation of myosin light-chain kinase leading to inactivation of Ca 2+ -sensitive pathways such as PKC and Rho-kinase [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Eicosapentaenoic acid ethyl ester improves endothelial dysfunction in type 2 diabetic mice

et al. 2018

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BackgroundEicosapentaenoic acid (EPA) is thought to have many beneficial effects, such as anti-atherosclerogenic and anti-inflammatory properties. However, few studies have reported its effects of endothelial dysfunction in diabetes and its direct effects on the aorta. Here, we investigated the effects of EPA treatment on impaired endothelium-dependent relaxation of the aorta in KKAy mice, a model of type 2 diabetes.MethodsMale KKAy mice were fed a high-fat (HF) diet for 8 weeks to induce diabetes, after which they were divided into two groups. One group was fed a HF diet, and the other group was fed a HF diet containing EPA ethyl ester (EPA-E, 10 mg/day) for 4 weeks. Then, the vascular reactivities of prepared aortic rings were measured in an organ bath to determine if EPA-E administration changed vascular function in these diabetic mice. In addition, we examined effect of EPA-E and its metabolites to vascular action using aorta separated from C57BL/6 J mice.ResultsAlthough EPA-E administration did not change the plasma glucose and insulin levels in diabetic mice, total cholesterol levels were significantly decreased. The aorta extracted from EPA-E untreated diabetic mice showed impaired endothelium-dependent relaxation in response to acetylcholine (ACh). However, EPA-E administration improved the relaxation response to ACh to the control levels observed in non-diabetic C57BL/6 J mice. On the other hand, endothelium-independent relaxation in response to sodium nitroprusside did not significantly differ among these three groups. The enhanced contractile response by phenylephrine in diabetic mice was not altered by the administration of EPA-E. In addition, the direct administration of EPA-E metabolites such as EPA, docosahexaenoic acid, and docosapentaenoic acid led to vasodilation in the aortic rings of C57BL/6 J mice.ConclusionThese results showed that chronic EPA-E administration prevented the development of endothelial dysfunction in KKAy mice, partly via the direct action of EPA-E metabolites on the aorta.

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Section: Discussionmentioning

confidence: 99%

Eicosapentaenoic acid ethyl ester improves endothelial dysfunction in type 2 diabetic mice

et al. 2018

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“…Aortic vascular function was measured as previously described [ 27 – 29 ]. Briefly, the thoracic aorta was quickly isolated and immersed in oxygenated, modified ice-cold bicarbonate-buffered physiologic salt solution (PSS; containing 137 mM NaCl, 4.73 mM KCl, 1.2 mM MgSO 4 , 0.025 mM EDTA, 1.2 mM KH 2 PO 4 , 2.5 mM CaCl 2 , and 11.1 mM glucose).…”

Section: Methodsmentioning

confidence: 99%

“…In this vasocontraction study, the normal physiological glucose concentration (11.1 mM) was defined as the normal glucose condition. To understand the direct effects of extracellular glucose accumulation, a high glucose condition was established by pretreating the vascular tissues with high glucose-PSS (22.2 mM glucose in PSS) at 37 °C for 30 min, as previously reported by our laboratory [ 29 ]. These values were based on reported postprandial glucose levels in C57BL/6 J (~ 11.1 mM) and KKAy mice (~ 22.2 mM) in vivo [ 30 , 31 ].…”

Section: Methodsmentioning

confidence: 99%

Effects of dietary palmitoleic acid on vascular function in aorta of diabetic mice

et al. 2022

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Background Chronic hyperglycemia in diabetes causes atherosclerosis and progresses to diabetic macroangiopathy, and can lead to coronary heart disease, myocardial infarction and cerebrovascular disease. Palmitoleic acid (POA) is a product of endogenous lipogenesis and is present in fish and vegetable oil. In human and animal studies, POA is reported as a beneficial fatty acid related to insulin sensitivity and glucose tolerance. However, few studies have reported its effects on aortic function in diabetes. Here, we investigated the effects of POA administration on vascular function in KKAy mice, a model of type 2 diabetes. Methods Male C57BL/6 J (control) and KKAy (experimental) mice at the age of 14 weeks were used in the present study. For each mouse strain, one group was fed with reference diet and a second group was fed POA-containing diet for 2 weeks. The vascular reactivities of prepared aortic rings were then measured in an organ bath to determine if POA administration changed vascular function in these mice. Results KKAy mice treated with POA exhibited decreased plasma glucose levels compared with mice treated with reference diet. However, endothelium-dependent vasorelaxant responses to acetylcholine and protease-activated receptor 2 activating protein, which are attenuated in the aorta of KKAy mice compared to C57BL/6 J mice under a reference diet, were not affected by a 2-week POA treatment. In addition, assessment of vasoconstriction revealed that the phenylephrine-induced vasoconstrictive response was enhanced in KKAy mice compared to C57BL/6 J mice under a reference diet, but no effect was observed in KKAy mice fed a POA-containing diet. In contrast, there was an increase in vasoconstriction in C57BL/6 J mice fed the POA-containing diet compared to mice fed a reference diet. Furthermore, the vasoconstriction in aorta in both C57BL/6 J and KKAy mice fed a POA-containing diet were further enhanced under hyperglycemic conditions compared to normal glucose conditions in vitro. In the hyperinsulinemic, and hyperinsulinemic combined with hyperglycemic conditions, vasoconstriction was increased in KKAy mice fed with POA. Conclusion These results suggest that POA intake enhances vasoconstriction under hyperglycemic and hyperinsulinemic conditions, which are characteristics of type 2 diabetes, and may contribute to increased vascular complications in diabetes.

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“…Aortic vascular function was measured as previously described [19][20][21]. Brie y, the thoracic aorta was quickly isolated and immersed in oxygenated, modi ed ice-cold bicarbonate-buffered physiologic salt solution (PSS; containing 137 mM NaCl, 4.73 mM KCl, 1.2 mM MgSO 4 , 0.025 mM EDTA, 1.2 mM KH 2 PO 4 , 2.5 mM CaCl 2 , and 11.1 mM glucose).…”

Section: Measurement Of Isometric Forcementioning

confidence: 99%

“…In this vasocontraction study, the normal physiological glucose concentration (11.1 mM) was de ned as the normal glucose condition. To understand the direct effects of extracellular glucose accumulation, a high glucose condition was established by pretreating the vascular tissues with high glucose-PSS (22.2 mM glucose in PSS) at 37°C for 30 minutes, as previously reported by our laboratory [21]. The obtained change in vascular tension was shown as the generated tension per 1 mm length of the aortic ring.…”

Section: Measurement Of Isometric Forcementioning

confidence: 99%

Effects of Dietary Palmitoleic Acid on Vascular Function in Aorta of Diabetic Mice

Takenouchi

Seki

Shiba

et al. 2021

Preprint

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BackgroundChronic hyperglycemia in diabetes causes atherosclerosis and progresses to diabetic macroangiopathy, and can lead to coronary heart disease, myocardial infarction and cerebrovascular disease. Palmitoleic acid (POA) is a product of endogenous lipogenesis and is present in fish and vegetable oil. In human and animal studies, POA is reported as a beneficial fatty acid related to insulin sensitivity and glucose tolerance. However, few studies have reported its effects on aortic function in diabetes. Here, we investigated the effects of POA administration on vascular function in KKAy mice, a model of type 2 diabetes.MethodsMale KKAy and C57BL/6J mice at the age of 14 weeks were used in the present study. For each mouse strain, one group was fed with normal diet and the other group was fed POA-containing diet for 2 weeks. Then, the vascular reactivities of prepared aortic rings were measured in an organ bath to determine if POA administration changed vascular function in these mice.ResultsKKAy mice treated with POA exhibited decreased plasma glucose levels compared with mice treated with normal diet. However, endothelium-dependent vasorelaxant responses to acetylcholine and protease-activated receptor 2 activating protein, which are attenuated in the aorta of KKAy mice compared to control C57BL/6J mice under a normal diet, were not affected by a 2-week POA treatment. In addition, assessment of vasoconstriction revealed that the phenylephrine-induced vasoconstrictive response was enhanced in KKAy mice compared to control mice under a normal diet, but no effect was observed in KKAy mice fed a POA-containing diet. In contrast, there was an increase in vasoconstriction in control mice fed the POA-containing diet compared to mice fed a normal diet. Furthermore, the vasoconstriction in aorta in both control and KKAy mice fed a POA-containing diet were further enhanced under hyperglycemic conditions compared to normal glucose conditions in vitro. In the hyperinsulinemic, and hyperinsulinemic combined with hyperglycemic conditions, vasoconstriction was increased in KKAy mice fed with POA.ConclusionThese results suggest that POA intake enhances vasoconstriction under hyperglycemic and hyperinsulinemic conditions, which are characteristics of type 2 diabetes, and may contribute to increased vascular complications in diabetes.

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Two Types of Overcontraction Are Involved in Intrarenal Artery Dysfunction in Type II Diabetic Mouse

Cited by 8 publications

References 30 publications

Eicosapentaenoic acid ethyl ester improves endothelial dysfunction in type 2 diabetic mice

Eicosapentaenoic acid ethyl ester improves endothelial dysfunction in type 2 diabetic mice

Effects of dietary palmitoleic acid on vascular function in aorta of diabetic mice

Effects of Dietary Palmitoleic Acid on Vascular Function in Aorta of Diabetic Mice

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