Diabetes Mellitus Induces Hyperreactivity of 5-Hydroxytryptamine (5-HT)-Induced Constriction in Human Internal Thoracic Artery and Is Associated with Increase in the Membrane Protein Level of 5-HT[2A] Receptor

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  • Shiba Tatsuo
    First Department of Pharmacology, Graduate School of Clinical Pharmacy, Kyushu University of Health and Welfare
  • Yokota Atsuko
    Department of Cardiovascular Surgery, Miyazaki Prefectural Nobeoka Hospital Department of Surgery, Faculty of Medicine, Miyazaki University
  • Gamoh Shuji
    First Department of Pharmacology, Graduate School of Clinical Pharmacy, Kyushu University of Health and Welfare
  • Tanaka-Totoribe Naoko
    First Department of Pharmacology, Graduate School of Clinical Pharmacy, Kyushu University of Health and Welfare
  • Kuwabara Masachika
    Kuwabara Clinic
  • Nakamura Eisaku
    Department of Surgery, Faculty of Medicine, Miyazaki University
  • Hayase Takahiro
    Department of Cardiovascular Surgery, Miyazaki Prefectural Nobeoka Hospital
  • Nakamura Kunihide
    Department of Surgery, Faculty of Medicine, Miyazaki University
  • Yamamoto Ryuichi
    First Department of Pharmacology, Graduate School of Clinical Pharmacy, Kyushu University of Health and Welfare

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  • Diabetes Mellitus Induces Hyperreactivity of 5-Hydroxytryptamine (5-HT)-Induced Constriction in Human Internal Thoracic Artery and Is Associated with Increase in the Membrane Protein Level of 5-HT<sub>2A</sub> Receptor

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<p>Studies indicate that 5-hydroxytryptamine (5-HT) released from activated platelets in coronary artery bypass grafting (CABG) induces 5-HT2A receptor-mediated graft spasm. We previously reported that 5-HT-induced constriction of human endothelium-denuded saphenous vein (SV) was significantly augmented in patients with diabetes mellitus (DM) than in patients without DM (non-DM), without changes in the levels of the membrane-bound 5-HT2A receptor of their smooth muscle cells. Although the internal thoracic artery (ITA) is the key graft conduit for CABG, the effect of DM on the ITA graft spasm is still unclear. Therefore, in this study, we investigated the effect of DM on 5-HT-induced vasoconstriction and the level of membrane-bound 5-HT2A receptor in ITA grafts. 5-HT-induced constriction of the isolated human endothelial-denuded ITA was significantly higher in patients with DM than in patients without DM. In addition, the level of the 5-HT2A receptor in the membrane fraction of human ITA smooth muscle cells was significantly higher in patients with DM than in those without DM. These results demonstrate that DM is a risk factor for CABG in both venous and arterial conduits, and that it differentially affects the level of the membrane-bound 5-HT2A receptor in the venous and arterial smooth muscle cells.</p>

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