Effects of Docosahexaenoic Acids on Vascular Cell Functions

本研究旨在探讨二十二碳六烯酸(DHA)对体外培养的主动脉平滑肌细胞功能的影响。体外培养的大鼠主动脉平滑肌细胞经DHA处理后，对血管紧张素Ⅱ诱导的细胞增殖率和细胞肥大无明显影响。采用易卒中自发性高血压大鼠(SHRSP)和血压正常的Wistar京都大鼠(WKY)分离的细胞，观察DHA对细胞内钙动力学和一氧化氮(NO)生成的影响。SHRSP组细胞内游离钙离子的静息浓度和峰值浓度显著高于血管紧张素II或5-羟色胺刺激的WKY组。DHA处理可显著抑制血管紧张素II和5-羟色胺诱导的WKY细胞内钙动力学变化，而SHRSP细胞对DHA处理无效。提示DHA通过电压依赖性的…抑制C^-2+-gt；内流更多第二信使运营的C^lt；2+频道，但不是商店运营的频道。SHRSP细胞经IL-1β诱导产生的总NO明显低于WKY细胞，DI-LA可显著增加IL-13b诱导的WKY细胞NO产生，而SHRSP细胞对DHA处理无效。用Western bloffing方法分析，NO生成量的增加是由于诱导型一氧化氮合酶蛋白诱导的刺激。这些研究表明，收缩激动剂引起的细胞内Ca~(2+)动力学改变和血管平滑肌细胞NO生成减少在SHRSP的病理生理过程中起一定作用。由于细胞内钙和NO在血管平滑肌细胞功能中起重要作用，因此改善这些功能的特性可能有助于DHA对心血管疾病的有益作用。较少

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