Studes on the L-arginine-derived, endothelium-independent relaxing factor

1.我们研究了内毒素是否参与了L-精氨酸诱导的内皮剥脱大鼠胸主动脉舒张，这似乎是由血管平滑肌中的一氧化氮合酶介导的.在没有内毒素的情况下，L-精氨酸几乎不引起任何动脉舒张。用内毒素处理动脉，响应于10 μ M L-精氨酸启动松弛，滞后期为2-4小时，并且松弛程度在重复应用L-精氨酸时增加，在几小时内达到一致的水平。内毒素浓度的增加缩短了滞后期，增强了舒张程度，降低了舒张动脉所需的L-精氨酸的阈值浓度。在内毒素致敏的动脉中，L-精氨酸在诱导舒张所需的浓度下刺激环GMP的产生。预防性应用放线菌素D或地塞米松，抑制一氧化氮合酶的诱导，防止L ...更多信息 - 精氨酸诱导的松弛和环GMP形成。多粘菌素B可抑制内毒素的作用，也可抑制L-精氨酸诱导的内毒素致敏的血管舒张和环鸟苷酸的形成。当使用去离子水制备Krebs溶液时，储库中的内毒素量高于启动L-精氨酸诱导的松弛和环GMP形成所需的水平。这些结果表明，内毒素通过在血管平滑肌表达一氧化氮合酶，触发了L-精氨酸诱导的血管舒张的时间依赖性发展.我们研究了酪氨酸激酶抑制剂对内毒素（LPS）引发的L-精氨酸诱导的大鼠胸主动脉舒张的影响。预防性应用酪氨酸激酶抑制剂除莠霉素A、染料木黄酮和erbstatin类似物选择性地阻止了LPS引起的L-精氨酸诱导的舒张和环GMP形成的起始。这些结果表明，酪氨酸激酶介导L-精氨酸诱导的动脉舒张，可能是通过LPS触发的信号通路中的蛋白酪氨酸磷酸化，触发诱导型NO合酶的表达，产生NO。

1. We examined whether endotoxin contributes to L-arginine-induced relaxation of endothelium-denuded rat thoracic aorta, which apears to be mediated by nitric oxide synthase in the vascular smooth muscle.2. In the absence of endotoxin, L-arginine induced scarcely any relaxation of the arteries. Treatment of the arteries with endotoxin initiated ralaxation in response to 10 muM L-arginine with lag periods of 2-4 hr, and degree of relaxation increased on repeated application of L-arginine to reach a consistent level in several hours. Increase in the concentration of endotoxin shortened the lag period, enhanced the degree of relaxation and lowered the threshold concentration of L-arginine required to relax the arteries. In endotoxin-primed arteries, L-arginine at concentrations necessary to induce relaxation stimulated cyclic GMP production.3. Prophylactic appliction of actinomycin D or dexamethasone, which inhibits induction of nitric oxide synthase, prevented induction by endotoxin of L … More -arginine-induced relaxation and cyclic GMP formation. Polymyxin B, which inhibits the action of endotoxin, also prevented development of endotoxin-sensitized relaxation and cyclic GMP formation inducded by L-arginine.4. When the Krebs solution was prepared using de-ionized water, the amount of endotoxin in the reservoir was above the level required to initiate L-arginine-induced relaxation and cyclic GMP fotmation.5. These results suggest that endotoxin triggered time-dependent development of L-arginine-induced relaxation by expressing nitric oxide synthase in the vascular smooth muscle.6. We examined the effects of tyrosine kinase inhibitors on the endotoxin(LPS)-primed, L-arginine-induced relaxation of rat thoracic aorta.7. Prophylactic application of the tyrosine kinase inhibitors herbimycin A, genistein and erbstatin analog selectively prevented the initiation by LPS of L-arginine-induced relaxation and cyclic GMP formation.8. These results suggest that tyrosine kinase mediates the L-arginine-induced relaxation of the arteries, probably through protein tyrosine phosphorylation in the LPS-triggered signaling pathway that triggers expression of an inducible NO synthase producing NO. Less