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

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Abstract

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) NG-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 P2Y6 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 P2Y6 receptor.

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Fig. 1
Fig. 2

Abbreviations

ACh:

Acetylcholine

COX:

Cyclooxygenase

EDCF:

Endothelium-derived contracting factor

EDRF:

Endothelium-derived relaxing factor

KHS:

Krebs–Henseleit Solution

LETO:

Long-Evans Tokushima Otsuka

L-NNA:

NG-nitro-L-arginine

NO:

Nitric oxide

NOS:

Nitric oxide synthase

OLETF:

Otsuka Long-Evans Tokushima Fatty

PE:

Phenylephrine

SNP:

Sodium nitroprusside

UDP:

Uridine 5′-diphosphate

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Acknowledgements

We thank T. Kamioka, S. Oshima, Y. Ohta, S. Ohashi, A. Ozeki, S. Takeno, M. Tani, and M. Tamura for technical assistance. This study was supported in part by JSPS KAKENHI Grant Numbers JP17K08318 and JP15K07975 and by the Suzuken Memorial Foundation (Japan). The authors would like to thank Enago (www.enago.jp) for the English language review.

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Author notes

  1. Shota Kobayashi and Takayuki Matsumoto contributed equally to this work and should be considered as co-first authors.

Authors and Affiliations

  1. Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo, 142-8501, Japan

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

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  1. Shota Kobayashi
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Correspondence to Tsuneo Kobayashi.

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Conflicts of interest

Shota Kobayashi declares that he has no conflict of interest.

Takayuki Matsumoto declares that he has no conflict of interest.

Makoto Ando declares that he has no conflict of interest.

Maika Iguchi declares that he/she has no conflict of interest.

Shun Watanabe declares that he has no conflict of interest.

Kumiko Taguchi declares that she has no conflict of interest.

Tsuneo Kobayashi declares that he has no conflict of interest.

Ethical approval

This study was approved by the Hoshi University Animal Care and Use Committee, and all studies were conducted in accordance with the Guide for the Care and Use of Laboratory Animals, published by the US National Institutes of Health, and the Guide for the Care and Use of Laboratory Animals adopted by the Committee on the Care and Use of Laboratory Animals of Hoshi University (accredited by the Ministry of Education, Culture, Sports, Science, and Technology, Japan).

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Kobayashi, S., Matsumoto, T., Ando, M. et al. UDP-induced relaxation is enhanced in aorta from female obese Otsuka Long–Evans Tokushima Fatty rats. Purinergic Signalling 14, 91–96 (2018). https://doi.org/10.1007/s11302-017-9595-y

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