Impaired endothelium-derived hyperpolarization-type relaxation in superior mesenteric arteries isolated from female Otsuka Long-Evans Tokushima Fatty rats

Matsumoto, Takayuki; Kobayashi, Shota; Ando, Makoto; Watanabe, Shun; Iguchi, Maika; Taguchi, Kumiko; Kobayashi, Tsuneo

doi:10.1016/j.ejphar.2017.03.062

Cited by 11 publications

(14 citation statements)

References 69 publications

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“…2B; Table 1). Under preserved EDHF signaling, for example, in the presence of L-NNA (10 −4 M) and indomethacin (10 −5 M), 6,50,51) we observed no differences in the ACh-mediated relaxation between the vehicle and indoxyl sulfate groups ( Fig. 2C; Table 1).…”

Section: Resultsmentioning

confidence: 81%

“…25,26) Of note, prostacyclin exerts both vasodilator and vasoconstrictor functions depending on factors mentioned above such as vessel types and (patho) physiological states. [19][20][21][22] In fact, we 6,50,52) observed an imbalance between endothelium-derived factors, such as reduced EDRF signaling and elevated EDCF signaling, in the superior mesenteric arteries of rats with diseases including diabetes. Thus, we used such arteries because the ACh-induced endotheliumdependent vascular responses were not only mediated by NO but also by EDHF and PGs.…”

Section: Resultsmentioning

confidence: 87%

“…Vascular Functional Study We determined the concentration-relaxation responses of the vascular function in the rat superior mesenteric arteries were determined by measuring the isometric force as previously reported. 6,[48][49][50][51] The superior mesenteric artery was quickly isolated and immersed in oxygenated, modified Krebs-Henseleit solution (KHS; containing 118.0-mM NaCl, 4.7-mM KCl, 25.0-mM NaHCO 3 , 1.8-mM CaCl 2 , 1.2-mM NaH 2 PO 4 , 1.2-mM MgSO 4 , and 11.0-mM glucose). Next, the artery was cleaned and cut into rings (2 mm in length) and suspended in a well-oxygenated (95% O 2 , 5% CO 2 ) bath containing 4 or 5 mL of KHS at 37°C.…”

Section: Animals Drugs and Materialsmentioning

confidence: 99%

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Direct Impairment of the Endothelial Function by Acute Indoxyl Sulfate through Declined Nitric Oxide and Not Endothelium-Derived Hyperpolarizing Factor or Vasodilator Prostaglandins in the Rat Superior Mesenteric Artery

Matsumoto

Takayanagi

Kojima

et al. 2019

Biological & Pharmaceutical Bulletin

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Upon stimulation, endothelial cells release various factors to regulate the vascular tone. In particular, vasorelaxing factors, called endothelium-derived relaxing factors (EDRFs), are altered in the production and/or release, as well as their signaling every vessel and under pathophysiological states, including cardiovascular, kidney, and metabolic diseases. Although indoxyl sulfate is known as a protein-bound uremic toxin and circulating levels are elevated in the impaired kidney functions, direct impact on the vascular function, especially EDRF's signaling, remains unclear. In this study, we hypothesize that acute exposure to indoxyl sulfate could alter vascular relaxation in the rat superior mesenteric artery. Accordingly, we measured acetylcholine (ACh)-induced endothelium-dependent relaxation in the absence and presence of several inhibitors to divide into each EDRF, including nitric oxide (NO), vasodilator prostaglandins (PGs), and endotheliumderived hyperpolarizing factor (EDHF). Indoxyl sulfate reduced the sensitivity to ACh but not sodium nitroprusside. Under cyclooxygenase (COX) inhibition or inhibitions of COX plus source of EDHF, such as small (SK Ca)-and intermediate (IK Ca)-conductance calcium-activated K channels, the decreased sensitivity to ACh in indoxyl sulfate exposed vessel was still preserved. However, under inhibition of NO synthase (NOS) or inhibitions of NOS and COX, the difference of sensitivity to ACh between vehicle and indoxyl sulfate was eliminated. These findings indicated that acute exposure of indoxyl sulfate in the rat superior mesenteric artery specifically explicitly impaired NO signaling but not EDHF or vasodilator PGs.

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Section: Resultsmentioning

confidence: 81%

Section: Resultsmentioning

confidence: 87%

Section: Animals Drugs and Materialsmentioning

confidence: 99%

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Direct Impairment of the Endothelial Function by Acute Indoxyl Sulfate through Declined Nitric Oxide and Not Endothelium-Derived Hyperpolarizing Factor or Vasodilator Prostaglandins in the Rat Superior Mesenteric Artery

Matsumoto

Takayanagi

Kojima

et al. 2019

Biological & Pharmaceutical Bulletin

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“…We very recently observed that the female OLETF rat at approximately 1 year of age manifests obesity, hypertension, hyperglycemia, hyperinsulinemia, and hyperlipidemia [28]. Endothelial dysfunction is observed in animals suffering from each of the above factors [31,32]; thus, in female OLETF rats aged 12 months, endothelial dysfunction may result from the long-term suffering of aforementioned phenomena.…”

Section: Resultsmentioning

confidence: 99%

“…In male OLETF rats, we [20][21][22][23][24] and others [25] demonstrated vascular dysfunction in several arteries. Conversely, in female OLETF rats, although reproductive or metabolic dysfunction were reported [19,26,27], we recently o b s e r v e d t h a t i m p a i r e d e n d o t h e l i u m -d e r i v e d , hyperpolarization-mediated relaxation was impaired in superior mesenteric arteries for this animal model [28]; no study has focused on the relationship between vascular function and nucleotides in female OLETF rats.…”

Section: Introductionmentioning

confidence: 99%

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

Kobayashi

Matsumoto

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.

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Impaired cross-talk between NO and hyperpolarization in myoendothelial feedback: a novel therapeutic target in early endothelial dysfunction of metabolic disease

Alaaeddine

Mroueh

Gust

et al. 2019

Current Opinion in Pharmacology

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Impaired endothelium-derived hyperpolarization-type relaxation in superior mesenteric arteries isolated from female Otsuka Long-Evans Tokushima Fatty rats

Cited by 11 publications

References 69 publications

Direct Impairment of the Endothelial Function by Acute Indoxyl Sulfate through Declined Nitric Oxide and Not Endothelium-Derived Hyperpolarizing Factor or Vasodilator Prostaglandins in the Rat Superior Mesenteric Artery

Direct Impairment of the Endothelial Function by Acute Indoxyl Sulfate through Declined Nitric Oxide and Not Endothelium-Derived Hyperpolarizing Factor or Vasodilator Prostaglandins in the Rat Superior Mesenteric Artery

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

Impaired cross-talk between NO and hyperpolarization in myoendothelial feedback: a novel therapeutic target in early endothelial dysfunction of metabolic disease

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