抑制 iNOS 可保护老年大鼠内皮依赖性血管舒张。
Inhibition of iNOS protects endothelial-dependent vasodilation in aged rats.
机构信息
Department of Physiology, Shanxi Medical University, Taiyuan, China.
出版信息
Acta Pharmacol Sin. 2010 Oct;31(10):1324-8. doi: 10.1038/aps.2010.111. Epub 2010 Sep 13.
AIM
To examine whether iNOS contributes to endothelial dysfunction in aged rats.
METHODS
Male Sprague Dawley rats were divided into three groups: young rats, aged rats treated with vehicle and aged rats treated with N-[3-(Aminomethyl) benzyl] acetamidine (1400W, 1 mg/kg, ip). Vasorelaxation was measured in isolated thoracic aorta. iNOS expression of thoracic aortic arteries was detected using immunohistochemistry and Western blot. Nitrotyrosine (a marker for peroxynitrite formation) content and expression in thoracic aortic tissue were determined using enzyme linked immunosorbent assay and immunohistochemistry.
RESULTS
Maximal relaxation induced by acetylcholine (10⁻⁹ to 10⁻⁵ mol/L) in the aged rats treated with vehicle was significantly decreased (70%±15%, P<0.01), as compared with the young rats (95%±8%). However, the maximal relaxation induced by acidified NaNO2 (an endothelium-independent vasodilator) had no significant difference between the two groups. Moreover, iNOS and nitrotyrosine expression increased in the vessels of the aged rats. In the aged rats treated with 1400W (a highly selective iNOS inhibitor) nitrotyrosine expression was reduced and acetylcholine-induced vasorelaxation was markedly improved (maximal relaxation was increased to 87%±8%, P<0.05), but the acidified NaNO₂-induced vasorelaxation had no significant change.
CONCLUSION
Our study demonstrated that inhibition of iNOS by 1400W increased endothelium-dependent vasodilation in aged rats. The mechanism was related with attenuation of peroxynitrite formation.
目的
观察诱导型一氧化氮合酶（iNOS）是否参与老年大鼠的内皮功能障碍。
方法
雄性 Sprague Dawley 大鼠分为三组：年轻大鼠、给予载体的老年大鼠和给予 N-[3-(氨甲基)苄基]乙脒（1400W，1mg/kg，腹腔注射）的老年大鼠。在分离的胸主动脉中测量血管舒张。使用免疫组织化学和 Western blot 检测胸主动脉中 iNOS 的表达。使用酶联免疫吸附试验和免疫组织化学检测胸主动脉组织中硝基酪氨酸（过氧亚硝酸盐形成的标志物）含量和表达。
结果
与年轻大鼠（95%±8%）相比，给予载体的老年大鼠（70%±15%，P<0.01）乙酰胆碱（10⁻⁹ 至 10⁻⁵mol/L）诱导的最大舒张明显降低。然而，两组之间酸化的 NaNO₂（一种内皮非依赖性血管扩张剂）诱导的最大舒张没有显著差异。此外，老年大鼠血管中 iNOS 和硝基酪氨酸的表达增加。在给予 1400W（一种高度选择性的 iNOS 抑制剂）的老年大鼠中，硝基酪氨酸的表达减少，乙酰胆碱诱导的血管舒张明显改善（最大舒张增加至 87%±8%，P<0.05），但酸化的 NaNO₂诱导的血管舒张没有明显变化。
结论
我们的研究表明，1400W 通过抑制 iNOS 增加了老年大鼠的内皮依赖性血管舒张。该机制与过氧亚硝酸盐形成的减少有关。
Zotero 插件