Ikeda U, Yamamoto K, Maeda Y, Shimpo M, Kanbe T, Shimada K
Department of Cardiology, Jichi Medical School, Tochigi, Japan.
Hypertension. 1997 Jan;29(1 Pt 1):65-9. doi: 10.1161/01.hyp.29.1.65.
We investigated the effects of endothelin-1 on nitric oxide synthesis in vascular smooth muscle cells. We measured the production of nitrite, a stable metabolite of nitric oxide, and the expression of inducible nitric oxide synthase mRNA and protein in cultured rat vascular smooth muscle cells. Incubation of the cultures with interleukin-1 beta (10 ng/mL) for 24 hours caused a significant increase in nitrite production. Endothelin-1 significantly decreased the interleukin-1 beta-induced nitrite production by vascular smooth muscle cells in a dose-dependent manner (10(-11) to 10(-8) mol/L). Incubation with interleukin-1 beta for 24 hours induced expression of inducible nitric oxide synthase mRNA and protein in vascular smooth muscle cells, whereas endothelin-1 showed a suppressive effect on their expressions. Addition of the endothelin type A receptor antagonist BQ-485, but not the endothelin type B receptor antagonist BQ-788, dose-dependently inhibited the effect of endothelin-1. After protein kinase C activity was functionally depleted by treatment of cells with phorbol 12-myristate 13-acetate for 24 hours, the effect of endothelin-1 was abolished. These results indicate that endothelin-1 acts on endothelin type A receptors and inhibits nitric oxide synthesis in interleukin-1 beta-stimulated vascular smooth muscle cells at least partially through a protein kinase C-dependent pathway.
我们研究了内皮素 -1 对血管平滑肌细胞中一氧化氮合成的影响。我们测量了一氧化氮的稳定代谢产物亚硝酸盐的生成量，以及培养的大鼠血管平滑肌细胞中诱导型一氧化氮合酶 mRNA 和蛋白的表达。用白细胞介素 -1β（10 ng/mL）孵育培养物 24 小时可导致亚硝酸盐生成量显著增加。内皮素 -1 以剂量依赖方式（10(-11) 至 10(-8) mol/L）显著降低白细胞介素 -1β 诱导的血管平滑肌细胞亚硝酸盐生成。用白细胞介素 -1β 孵育 24 小时可诱导血管平滑肌细胞中诱导型一氧化氮合酶 mRNA 和蛋白的表达，而内皮素 -1 对其表达具有抑制作用。添加内皮素 A 型受体拮抗剂 BQ -485 可剂量依赖性抑制内皮素 -1 的作用，而内皮素 B 型受体拮抗剂 BQ -788 则无此作用。在用佛波酯 12 -肉豆蔻酸 13 -乙酸酯处理细胞 24 小时使蛋白激酶 C 活性功能缺失后，内皮素 -1 的作用被消除。这些结果表明，内皮素 -1 作用于内皮素 A 型受体，并至少部分通过蛋白激酶 C 依赖性途径抑制白细胞介素 -1β 刺激的血管平滑肌细胞中的一氧化氮合成。
