Department of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Towada City, Aomori 034-8628, Japan.
Biochem Biophys Res Commun. 2010 Mar 19;393(4):668-72. doi: 10.1016/j.bbrc.2010.02.053. Epub 2010 Feb 17.
Omentin is a recently identified adipose tissue-derived cytokine and is implicated in obesity-related cardiovascular disorders. In the present study, we tested the hypothesis that omentin could directly affect vascular reactivity of isolated blood vessels. In endothelium-intact rat isolated aorta, pretreatment with omentin (300 ng/ml, 30 min) inhibited noradrenaline (NA; 1 nM-1 microM)-induced concentration-dependent contraction. In NA (100 nM)-pre-contracted aorta, omentin (1-300 ng/ml) directly induced an endothelium-dependent relaxation. While a nitric oxide (NO) synthase (NOS) inhibitor, N(G)-nitro-l-arginine methyl ester (100 microM, 30 min) inhibited the relaxation, a PI3K/Akt inhibitor, LY294002 (10 microM, 30 min) or a tyrosine kinase inhibitor, genistein (30 microM, 30 min) was ineffective. Omentin (300 ng/ml, 5 min) induced a phosphorylation of endothelial NOS at serine 1177 but not a phosphorylation of Akt at serine 473. Omentin (1-300 ng/ml) also relaxed NA pre-contracted mesenteric artery. Present study for the first time demonstrated that omentin has a vasodilating effect on isolated blood vessels, which is mediated through endothelium-derived NO.
网膜素是一种新近发现的脂肪组织来源的细胞因子，与肥胖相关的心血管疾病有关。本研究旨在验证网膜素有否直接影响血管的反应性。在血管内皮完整的大鼠离体主动脉中，预先用网膜素（300ng/ml，30 分钟）孵育可抑制去甲肾上腺素（NA；1 nM-1 μM）浓度依赖性收缩。在预先用 NA（100 nM）收缩的主动脉中，网膜素（1-300ng/ml）可直接诱导内皮依赖性舒张。一氧化氮合酶（NOS）抑制剂 N(G)-硝基-l-精氨酸甲酯（100μM，30 分钟）可抑制舒张，但磷脂酰肌醇 3-激酶/蛋白激酶 B（PI3K/Akt）抑制剂 LY294002（10μM，30 分钟）或酪氨酸激酶抑制剂金雀异黄素（30μM，30 分钟）无效。网膜素（300ng/ml，5 分钟）可诱导内皮型 NOS 丝氨酸 1177 磷酸化，但不能诱导 Akt 丝氨酸 473 磷酸化。网膜素（1-300ng/ml）还可舒张预先用 NA 收缩的肠系膜动脉。本研究首次证明网膜素有舒张离体血管的作用，该作用是通过内皮衍生的一氧化氮介导的。
