RELATIVE ARGININE DEFICIENCY IN PULMONARY HYPERTENSION: PLT STDY-SUPPLEMENTATION

肺动脉高压中的相对精氨酸缺乏：PLT STDY 补充

• 批准号: 7377773
• 负责人: David B. Badesch
• 金额: $ 0.06万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7377773
• 关键词: RELATIVE; ARGININE; DEFICIENCY; PULMONARY; HYPERTENSION

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This project is being undertaken to test the hypothesis that arginine supplementation is safe and well-tolerated in patients with pulmonary hypertension (PH), and serves as a pilot study toward testing the hypothesis that patients with PH have a chronic relative deficiency of nitric oxide (NO) synthase substrate (arginine - arg). We hope to ultimately test the specific hypothesis that chronic supplementation with oral L-arginine would lead to clinical improvement in PH as measured by exercise capacity and cardiopulmonary hemodynamics. This work could define simple, inexpensive, low risk measures which might contribute to the treatment of PH. PH affects patients of all ages, both sexes (with a predilection toward young females), is highly lethal, and frequently requires complicated forms of therapy. Primary pulmonary hypertension (PPH) was previously rare, but the incidence appears to have recently increased in association with the widespread use of appetite-suppressant medications. PH occurring in association with scleroderma is less rare, and the development of PH has a substantial impact on long-term prognosis. Treatment of PH has improved over the past 10 years with the advent of high-dose calcium channel blocker therapy, continuously-infused prostacyclin, and lung transplantation. However, the large majority of patients do not respond favorably to calcium channel blockers, and prostacyclin therapy and lung transplantation are highly complicated and expensive. Recognition of the importance of NO as a vasodilator was followed by observations indicating its contribution to maintenance of normal vascular function. In addition to its action as a vasodilator, several studies suggest that nitric oxide exerts important effects on vascular structure. Inhaled NO is a potent pulmonary vasodilator. It has been shown to be of benefit in persistent PH of the newborn (PPHN). Although a small number of adult patients with PH have received chronic inhaled NO, some with apparent benefit; long-term delivery of inhaled NO to adults with PH has not been formally studied. Long-term delivery is expensive and complicated, and toxicology studies remain to be performed. Supplemental arginine improves endothelial dilator responses in human coronary artery disease. Recent work points to arginine-induced restoration of deficient endothelial function in diabetes, peripheral vascular disease and aging. Whether chronic arg supplementation can reduce ongoing vascular injury and lead to structural improvement in the lung circulation in patients with PH is unknown. This project will be randomized, placebo-controlled, and double-blinded pilot study of the safety of arginine supplementation in patients with PH. Efficacy will also be assessed as part of this pilot study, looking for trends toward improvement in exercise capacity and hemodynamics.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。本项目旨在验证精氨酸补充剂在肺动脉高压（PH）患者中安全且耐受性良好的假设，并作为一项初步研究，旨在验证PH患者一氧化氮（NO）合酶底物（精氨酸- arg）慢性相对缺乏的假设。我们希望最终测试的具体假设，长期补充口服L-精氨酸将导致PH的临床改善，通过运动能力和心肺血流动力学测量。这项工作可以定义简单，廉价，低风险的措施，这可能有助于治疗PH。PH影响所有年龄段的患者，男女（对年轻女性的偏好），是高度致命的，往往需要复杂的治疗形式。原发性肺动脉高压（PPH）以前是罕见的，但最近的发病率似乎增加了与广泛使用的食欲抑制药物。与硬皮病相关的PH发生并不罕见，PH的发展对长期预后有重大影响。在过去的10年里，随着高剂量钙通道阻滞剂治疗、持续输注前列环素和肺移植的出现，PH的治疗得到了改善。然而，大多数患者对钙通道阻滞剂反应不佳，前列环素治疗和肺移植非常复杂和昂贵。 认识到NO作为血管扩张剂的重要性之后，观察表明其对维持正常血管功能的贡献。除了作为血管扩张剂的作用外，一些研究表明一氧化氮对血管结构发挥重要作用。吸入NO是一种有效的肺血管扩张剂。它已被证明是有益的新生儿持续PH（PPHN）。尽管少数PH成人患者接受了慢性吸入NO，但有些患者具有明显的益处;长期吸入NO治疗PH成人尚未正式研究。长期输送既昂贵又复杂，毒理学研究仍有待进行。 补充精氨酸改善冠心病患者内皮扩张反应。最近的工作指出，精氨酸可诱导糖尿病、外周血管疾病和衰老中内皮功能缺陷的恢复。长期补充精氨酸是否可以减少正在进行的血管损伤，并导致PH患者肺循环的结构改善尚不清楚。 该项目将是一项随机、安慰剂对照、双盲的初步研究，旨在评估精氨酸补充剂在PH患者中的安全性。作为该初步研究的一部分，还将评估疗效，以寻找运动能力和血流动力学改善的趋势。