Effects of Docosahexaenoic Acids on Vascular Cell Functions

二十二碳六烯酸对血管细胞功能的影响

• 批准号: 09672244
• 负责人: HIRAFUJI Masahiko
• 金额: $ 2.05万
• 依托单位: Health Sciences University of Hokkaido
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09672244/
• 关键词: docosahexaenoic acid; vascular smooth muscle cells; intracellular calcium; nitric oxide; calcium channels; 5-hydroxytryptamine; angiotensin II; 高血圧症; ラット; 血管内皮細胞

The aim of the present project was to investigate the effects of docosahexaenoic acids (DHA) on vascular cells functions, using cultured aortic smooth muscle cells. Treatment of rat aortic smooth muscle cells with DHA in culture had no significant effect on the cell growth rate and cell hypertrophy induced by angiotensin II.The effects of DHA on intracellular C^<2+> dynamics and nitric oxide (NO) production were also examined using cells isolated from stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar Kyoto rats (WKY). The resting and peak concentrations of intracellular C^<2+> were significantly higher in cells from SHRSP than in WKY stimulated with angiotensin II or 5-hydroxytryptamine (5-HT). DHA treatment significantly suppressed the intracellular C^<2+> dynamics induced by angiotensin II and 5-HT in cells from WKY, while the cells from SHRSP were refractory to DHA treatment. It was suggested that DHA inhibited C^<2+> influx through the voltage-dependent o … More r 2nd messenger-operated C^<2+> channels, but not store-operated channels. The total NO production induced by interleukin-1beta (IL-1beta) was significantly lower in cells from SHRSP than from WKY.DI-LA treatment significantly increased IL-l3b-induced NO production in cells from WKY, while the cells from SHRSP were refractory to DHA treatment. The increase in NO production was due to the stimulation of inducible NO synthase protein induction, as analyzed by Western bloffing method. It is also suggested that DHA treatment can prevent cell damage evoked by IL-lbeta-induced NO.These studies suggest that the altered intracellular C^<2+> dynamics induced by contractile agonists and the diminished NO production in vascular smooth muscle cells play a role in the pathophysiology of SHRSP.Since the intracellular Ca and NO plays an important role in vascular smooth muscle cell functions, the properties to improve these functions can be contributed to the beneficial effect of DHA on cardiovascular disorders. Less

本研究的目的是利用培养的主动脉平滑肌细胞研究二十二碳六烯酸（DHA）对血管细胞功能的影响。用DHA处理培养的大鼠主动脉平滑肌细胞对血管紧张素II诱导的细胞生长速率和细胞肥大没有显著影响。DHA对细胞内C^<2+>动力学和一氧化氮（NO）产生的影响也用分离自易卒中的自发性高血压大鼠（SHRSP）和血压正常的Wistar京都大鼠（WKY）的细胞进行了检测。在血管紧张素II或5-羟色胺（5-HT）刺激的SHRSP细胞中，细胞内C^<2+>的静息浓度和峰值浓度显著高于WKY细胞。在WKY细胞中，DHA处理显着抑制了血管紧张素II和5-HT诱导的细胞内C^<2+>动力学，而SHRSP细胞对DHA处理不敏感。提示DHA通过电压依赖性的膜电位抑制C^<2+>内流。 ...更多信息 r第二信使操作的C^<2+>信道，但不是商店操作的信道。IL-1 β诱导的SHRSP细胞NO生成量显著低于WKY细胞，DI-LA处理显著增加IL-13 β诱导的WKY细胞NO生成量，而SHRSP细胞对DHA处理无效。通过Western bloffing方法分析，NO产生的增加是由于诱导型NO合酶蛋白诱导的刺激。这些研究表明，由收缩激动剂引起的细胞内C^<2+>动力学改变和血管平滑肌细胞中NO产生的减少在SHRSP的病理生理中起作用。由于细胞内Ca和NO在血管平滑肌细胞功能中起重要作用，改善这些功能的特性有助于DHA对心血管疾病的有益作用。少

项目成果

Hirafuji, M., Minami, M., Ebihara, T., Kawahara, F., Yoshioka, M., Saito, H.and Parvez, H.S.: Changes in intracellular Ca2+ signaling induced by docosahexaenoic acid in vascular smooth muscle cells from a genetical hypertensive rat(SHRSP), In Progress in

Hirafuji，M.，Minami，M.，Ebihara，T.，Kawahara，F.，Yoshioka，M.，Saito，H.和 Parvez，H.S.：二十二碳六烯酸在血管平滑肌细胞中诱导的细胞内 Ca2 信号传导的变化

平藤 雅彦: "血管平滑筋細胞機能に対するドコサヘキサエン酸の特異的調節作用" 日本薬理学雑誌. 110(補1). 171P-176P (1997)

Masahiko Hirafuji：“二十二碳六烯酸对血管平滑肌细胞功能的特异性调节作用”日本药理学杂志110（增刊1）（1997）。

Hirafuji, M., Ebihara, T., Kawahara, F.and Minami, M.: "Effect of docosahexaenoic acid on smooth muscle cell functions." Life Sci.62. 1689-1693 (1998)

Hirafuji, M.、Ebihara, T.、Kawahara, F. 和 Minami, M.：“二十二碳六烯酸对平滑肌细胞功能的影响。”

Hirafuji, M.: "Effect of docosahexaenoic acid on intracellular colcium dynamics in vascular smooth muscle cell from normotensive and geretically hypertersive rats" Res.Comm.Mol.Pathol.Pharmacd.102(1). 29-42 (1998)

Hirafuji, M.：“二十二碳六烯酸对正常血压和老年高血压大鼠血管平滑肌细胞内胆动态的影响”Res.Comm.Mol.Pathol.Pharmacd.102(1)。

Hirafuji, M., Kanai, Y., Tsunoda, M., Ebihara, T., Kawahara, F.and Minami, M.: Nitric Oxide Production by Vascular Smooth Muscle Cells From Stroke-prone Spontaneously Hypertensive Rats, In, The Biology of Nitric Oxide, Part 6. Ed.by Moncada, S., Toda, N.,

Hirafuji, M.、Kanai, Y.、Tsunoda, M.、Ebihara, T.、Kawahara, F. 和 Minami, M.：易中风自发性高血压大鼠的血管平滑肌细胞产生一氧化氮，《生物学》