Effects of inhaled oxide on regional blood flow are consistent with intravascular nitric oxide delivery
Effects of inhaled oxide on regional blood flow are consistent with intravascular nitric oxide delivery
复制标题
DOI：
10.1172/jci200112761
复制
发表时间：
2001-07-01
影响因子：
15.9
通讯作者：
Gladwin, MT
中科院分区：
文献类型：
--
作者：
Cannon, RO;Schechter, AN;Gladwin, MT
一氧化氮（NO）可以通过与血红蛋白结合，通过亚硝基化含巯基的血浆分子，或通过转化为亚硝酸盐来稳定，所有反应都可能保留其在血液中的生物活性。在这里，我们研究了血液运输的NO区域血管紧张度在人类吸入NO之前和期间的贡献。分别在呼吸室内空气和吸入NO浓度为百万分之80的室内空气的同时，测量16名受试者在静息状态和用N-G-单甲基-L-精氨酸（L-NMMA）阻断前臂NO合成后的前臂血流量，然后进行前臂运动应激。L-NMMA减少了25%的血流量，增加了50%的阻力，这一作用被NO吸入所阻断。在NO吸入的情况下，在休息和重复的握力运动期间，L-NMMA输注期间的阻力显著降低。S-亚硝基血红蛋白和血浆S-亚硝基硫醇没有改变与NO吸入。动脉亚硝酸盐水平增加了11%，动脉亚硝酰（血红素）血红蛋白水平增加了10倍，达到微摩尔范围，这两项措施在动脉中始终高于静脉血。S-亚硝基血红蛋白水平在纳摩尔范围内，没有明显的动脉-静脉梯度。这些结果表明，在阻断局部NO合成的同时吸入NO可以提供血管内NO以维持正常的血管功能。这种效应可能适用于治疗以内皮功能障碍为特征的疾病。
Nitric oxide (NO) may be stabilized by binding to hemoglobin, by nitrosating thiol-containing plasma molecules, or by conversion to nitrite, all reactions potentially preserving its bioactivity in blood. Here we examined the contribution of blood-transported NO to regional vascular tone in humans before and during NO inhalation. While breathing room air and then room air with NO at 80 parts per million, forearm blood flow was measured in 16 subjects at rest and after blockade of forearm NO synthesis with N-G-monomethyl-L-arginine (L-NMMA) followed by forearm exercise stress. L-NMMA reduced blood flow by 25% and increased resistance by 50%, an effect that was blocked by NO inhalation. With NO inhalation, resistance was significantly lower during L-NMMA infusion, both at rest and during repetitive hand-grip exercise. S-nitrosohemoglobin and plasma S-nitrosothiols did not change with NO inhalation. Arterial nitrite levels increased by 11% and arterial nitrosyl(heme)hemoglobin levels increased tenfold to the micromolar range, and both measures were consistently higher in the arterial than in venous blood. S-nitrosohemoglobin levels were in the nanomolar range, with no significant artery-to-vein gradients. These results indicate that inhaled NO during blockade of regional NO synthesis can supply intravascular NO to maintain normal vascular function. This effect may have application for the treatment of diseases characterized by endothelial dysfunction.