Ikeda U, Ikeda M, Minota S, Shimada K
Department of Cardiology, Jichi Medical School, Minamikawachi, Tochigi,Japan.
Circulation. 1999 Mar 9;99(9):1230-5. doi: 10.1161/01.cir.99.9.1230.
Elevated plasma homocysteine levels have been reported to be an independent risk factor for vascular disease. However, there have been no reports concerning the effects of homocysteine on the production of nitric oxide (NO), another modulator of vascular function and proliferation, by the vascular smooth muscle.
We investigated the effects of homocysteine on NO synthesis by measuring the production of nitrite, a stable metabolite of NO, in cultured rat vascular smooth muscle cells (VSMCs). Incubation of cultures with interleukin (IL)-1beta 10 ng/mL for 24 hours caused a significant increase in nitrite generation. The IL-1beta-induced nitrite production by VSMCs was significantly increased by homocysteine in a dose-dependent manner. This effect of homocysteine was significantly inhibited in the presence of NG-monomethyl-L-arginine or actinomycin D. The homocysteine-induced nitrite production was accompanied by increased inducible NO synthase mRNA and protein accumulation. Cysteine, glutathione, or hydrogen peroxide also increased nitrite accumulation in IL-1beta-stimulated VSMCs. Coincubation with the radical scavenger catalase or superoxide dismutase markedly reduced homocysteine-induced nitrite accumulation.
Homocysteine enhances NO synthesis in IL-1beta-stimulated VSMCs, and oxidative products are involved in the effect of homocysteine.
血浆同型半胱氨酸水平升高据报道是血管疾病的一个独立危险因素。然而，尚无关于同型半胱氨酸对血管平滑肌产生一氧化氮（NO）（血管功能和增殖的另一种调节因子）影响的报道。
我们通过测量培养的大鼠血管平滑肌细胞（VSMC）中亚硝酸盐（NO的一种稳定代谢产物）的生成来研究同型半胱氨酸对NO合成的影响。用10 ng/mL白细胞介素（IL）-1β孵育培养物24小时导致亚硝酸盐生成显著增加。同型半胱氨酸以剂量依赖方式显著增加VSMC中IL-1β诱导的亚硝酸盐生成。在存在NG-单甲基-L-精氨酸或放线菌素D的情况下，同型半胱氨酸的这种作用被显著抑制。同型半胱氨酸诱导的亚硝酸盐生成伴随着诱导型NO合酶mRNA和蛋白质积累增加。半胱氨酸、谷胱甘肽或过氧化氢也增加了IL-1β刺激的VSMC中亚硝酸盐积累。与自由基清除剂过氧化氢酶或超氧化物歧化酶共同孵育显著降低了同型半胱氨酸诱导的亚硝酸盐积累。
同型半胱氨酸增强IL-1β刺激的VSMC中NO合成，氧化产物参与同型半胱氨酸的作用。
