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

一氧化氮在内皮介导的 P 物质血管舒张中的作用

• 批准号: 3779630
• 负责人: J A PANZA
• 金额: --
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3779630
• 关键词: arginine; cardiovascular pharmacology; essential hypertension; human subject; nitric oxide; plethysmography; substance P; vascular endothelium; vasodilatation; vasodilators; vasomotion

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.

我们已经证明，原发性高血压患者的 内皮依赖的血管对P物质的反应 显示高血压患者的内皮功能障碍是 与一氧化氮系统的缺陷有关。然而， 一氧化氮在内皮依赖性血管扩张中的作用 对P物质的作用还没有在人类身上进行过研究。要解决这个问题 问题，我们研究了P物质治疗前后的反应 L精氨酸治疗高血压病8例 患者组和8例正常对照组。L是一种精氨酸类似物， 竞争性地抑制内皮细胞合成一氧化氮。 因此，使用这种物质可以研究一氧化氮 血管生理和病理生理调节中的系统 语气。药物被注入到臂动脉和前臂血液中 流量测量采用应变计体积描记法。如前所述， 血管扩张剂对P物质的反应显著抑制 高血压患者与正常对照组比较。L-NMMA显著 使正常人和高血压患者对P物质的反应迟钝 病人。然而，反应的抑制程度 正常对照组P物质含量明显高于正常对照组。 因此，当输注L-NMMA后对P物质的反应是 与正常人相比，患者与正常人之间无明显差异。因此， 这些发现表明P物质对人体的血管扩张作用。 至少部分是通过释放内皮源性一氧化氮来实现的 氧化物。对P物质反应的均衡化 L-NMMA给药对一氧化氮的抑制作用 综合表明，对P物质的反应受损 高血压患者与血管内皮细胞合成缺陷或 一氧化氮的释放。