ROLE OF NITRIC OXIDE IN THE ENDOTHELIUM-MEDIATED VASODILATION TO SUBSTANCE P

我们已经证明，原发性高血压患者 内皮依赖性血管对P物质的反应。我们还 显示高血压患者的内皮功能障碍是 与一氧化氮系统水平的缺陷有关。 然而，在这方面， 一氧化氮在内皮依赖性血管舒张中作用 尚未在人体中进行过研究。 为了解决这个 在这一问题上，我们研究了P物质的反应前后， NG-单甲基-L-精氨酸（L-NMMA）治疗高血压病8例 正常对照组8例。 L-NMMA是精氨酸类似物， 竞争性地抑制内皮合成一氧化氮。 因此，这种物质的使用允许研究一氧化氮 系统在血管生理和病理生理调节中的作用 语气 将药物注入肱动脉和前臂血液中 通过应变计体积描记法测量流量。 如前所述， P物质的血管舒张反应显著降低， 高血压患者与正常对照组比较。 L-NMMA显著 减弱了正常人和高血压患者对P物质的反应 患者 然而，抑制反应的程度 P物质的L-NMMA显着高于正常对照组。 因此，当输注L-NMMA后对P物质的反应是 与正常人相比，患者组与正常人组之间无显著性差异。 因此，在本发明中， 这些发现表明P物质在人体内具有血管扩张作用 至少部分由内皮源性一氧化氮释放介导 环氧 对P物质反应的均衡化， 给予L-NMMA并因此抑制一氧化氮 合成表明，受损的反应，P物质的 高血压患者与内皮合成缺陷有关， 释放一氧化氮。

We have shown that patients with essential hypertension have a reduced endothelium-dependent vascular response to substance P. We have also shown that the endothelial dysfunction of hypertensive patients is related to a defect at the level of the nitric oxide system. However, the contribution of nitric oxide to endothelium-dependent vasodilation to substance P has not been investigated in humans. To address this issue, we studied the response to substance P before and after administration of NG-monomethyl-L-arginine (L-NMMA) in 8 hypertensive patients and 8 normal controls. L-NMMA is an arginine analogue that competitively inhibits the synthesis of nitric oxide by the endothelium. Thus, the use of this substance permits the study of the nitric oxide system in the physiologic and pathophysiologic regulation of vascular tone. Drugs were infused into the brachial artery and the forearm blood flow was measured by strain gauge plethysmography. As shown before, the vasodilator response to substance P was significantly depressed in hypertensive patients compared to normal controls. L-NMMA significantly blunted the response to substance P in normals and in hypertensive patients. However, the magnitude of inhibition of the response to substance P by L-NMMA was significantly greater in the normal controls. Therefore, when the response to substance P after infusion of L-NMMA was compared, there was no difference between patients and normals. Thus, these findings indicate the vasodilator effect of substance P in humans is at least partly mediated by the release of endothelium-derived nitric oxide. The equalization of the response to substance P after administration of L-NMMA and therefore inhibition of nitric oxide synthesis indicates that the impaired response to substance P of hypertensive patients is related to a defect in endothelial synthesis or release of nitric oxide.