Fleming I, Gray G A, Julou-Schaeffer G, Parratt J R, Stoclet J C
Laboratoire de Pharmacologie Cellulaire et Moléculaire, Université Louis Pasteur de Strasbourg, CNRS URA 600, Illkirch, France.
Biochem Biophys Res Commun. 1990 Sep 14;171(2):562-8. doi: 10.1016/0006-291x(90)91183-s.
Rat aortic rings incubated with a low dose of endotoxin (100 ng ml-1) for 5 h exhibited depressed reactivity to norepinephrine (NE) which was independent of the presence of endothelium. An inhibitor of nitric oxide synthesis from L-arginine NGmonomethyl-L-arginine (300 microM), but not the inactive D-enantiomer, restored the contractile response of endotoxin-treated rings to control. The effect of NGmonomethyl-L-arginine was reversed by L-arginine (1 mM). In the absence of NGmonomethyl-L-arginine, L- but not D-arginine relaxed endotoxin-treated rings but was without effect on control tissues. This response was reversed following inhibition of guanylate cyclase by methylene blue (3 microM). In addition, tissue cyclic GMP content was 10 times greater in endotoxin-treated compared to control tissue. These data indicate that endotoxin can act directly on vascular tissue to induce a hyporeactivity to NE which is secondary to the activation of the L-arginine pathway and subsequent activation of soluble guanylate cyclase.
用低剂量内毒素（100 ng/ml）孵育5小时的大鼠主动脉环，对去甲肾上腺素（NE）的反应性降低，且这种反应与内皮细胞的存在无关。L-精氨酸一氧化氮合成抑制剂NG-单甲基-L-精氨酸（300 μM）可恢复内毒素处理环的收缩反应至对照水平，而无活性的D-对映体则无此作用。L-精氨酸（1 mM）可逆转NG-单甲基-L-精氨酸的作用。在没有NG-单甲基-L-精氨酸的情况下，L-精氨酸而非D-精氨酸可使内毒素处理的环舒张，但对对照组织无影响。亚甲蓝（3 μM）抑制鸟苷酸环化酶后，这种反应被逆转。此外，与对照组织相比，内毒素处理组织中的环磷酸鸟苷（cGMP）含量高10倍。这些数据表明，内毒素可直接作用于血管组织，诱导对NE的反应性降低，这是L-精氨酸途径激活及随后可溶性鸟苷酸环化酶激活的继发结果。
