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| 基本情報 |
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| 氏名 |
兒玉 朋子 |
| 氏名（カナ） |
ｺﾀﾞﾏ ﾄﾓｺ |
| 氏名（英語） |
Kodama Tomoko |
| 所属 |
獣医学部 獣医学科 |
| 職名 |
助教 |
| researchmap研究者コード |
R000034570 |
| researchmap機関 |
岡山理科大学 |
Adipocytokine, progranulin, augments acetylcholine-induced nitric oxide-mediated relaxation through the increases of cGMP production in rat isolated mesenteric artery
K. Kazama, K. Hoshino, T. Kodama, M. Okada, H. Yamawaki
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Aim: Progranulin (PGRN) is a novel adipocytokine with anti-inflammatory effects in vascular cells. The aim of this study was to clarify the effects of PGRN on reactivity of isolated blood vessel. Methods: Isometric contraction of rat isolated superior mesenteric artery was measured. Results: Pre-treatment with PGRN (10–100 ng mL−1, 30 min) had no effect on noradrenaline- or 5-hydroxytriptamine-induced contraction. On the other hand, pre-treatment with PGRN (100 ng mL−1) augmented acetylcholine (ACh; 30 nm)-induced endothelium-dependent relaxation. Pre-treatment with PGRN (100 ng mL−1) augmented ACh (10 μm)-induced nitric oxide (NO)-mediated relaxation in the presence of indomethacin (10 μm), a cyclooxygenase inhibitor, and tetraethyl ammonium (10 mm), a non-selective potassium channel blocker. In contrast, pre-treatment with PGRN (100 ng mL−1) had no effect on ACh-induced endothelium-derived hyperpolarizing factor-mediated relaxation. Pre-treatment with PGRN (100 ng mL−1) had no effect on ACh (10 μm, 1 min)-induced endothelial NO synthase phosphorylation (at Ser1177) as determined by Western blotting. Pre-treatment with PGRN (100 ng mL−1) augmented an NO donor, sodium nitroprusside (SNP; 30 nm–1 μm)- but not a membrane-permeable cGMP analogue, 8-bromo-cGMP-induced relaxation. In the presence of 3-isobutyl-1-methylxanthine (100 μm), a phosphodiesterase inhibitor, pre-treatment with PGRN (100 ng mL−1) increased SNP (30 nm, 5 min)-induced cGMP production as determined by enzyme immunoassay. Conclusion: We for the first time demonstrate that PGRN augments ACh-induced NO-mediated relaxation through the increases of cGMP production in smooth muscle. These results indicate PGRN as a possible pharmacotherapeutic target against cardiovascular diseases including obesity-related hypertension.
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