Nitric Oxide and Oxygen Delivery Among Tibetans

藏族人的一氧化氮和氧气输送

• 批准号: 0215747
• 负责人: Cynthia Beall
• 金额: --
• 依托单位: Case Western Reserve University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至 2008-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0215747&HistoricalAwards=false
• 关键词: Nitric; Oxide; Oxygen; Delivery; Among

This project will investigate a newly proposed mechanism by which humans can adapt to life in an extreme environment. Tibetans have lived at high altitudes for millennia and have been demonstrated to possess a number of adaptations for dealing with life on the Tibetan Plateau and in the Himalayan Mountains. The proposed research is designed to test the hypothesis that the high levels of exhaled nitric oxide produced by Tibetan high-altitude natives are responses that improve functional capacity in their environment where there are fewer oxygen molecules in every breath, a situation called high-altitude hypoxia. Based on the known effects of nitric oxide, it is hypothesized that high levels of nitric oxide in the lungs helps in two ways. First, it may offset the high-altitude hypoxia by enabling the extraction of a larger proportion of the oxygen in the inspired air. Second, it may improve oxygen delivery by increasing blood flow throughout the body. The recent finding that high-altitude native Tibetans exhale more than twice as much nitric oxide as sea-level natives at sea level requires explanation because a large body of evidence predicts less, rather than more, synthesis of nitric oxide under hypoxic conditions. The consistent finding of high pulmonary nitric oxide in both Tibetan and Andean indigenous high-altitude populations suggests an adaptive, beneficial function. The hypotheses will be tested with a sample of 91 high-altitude natives of the Tibet Autonomous Region living at 4200m (~ 14,000') altitude. The study participants will be healthy, not pregnant, non-smokers, 18-55 years of age. The concentration of nitric oxide in exhaled breath will be measured and it is expected that there will be a wide range of variation including values two to three times higher than those found at sea level. The hypothesis of greater oxygen extraction will be tested by measuring the difference in the percent of oxygen in inspired air (20.9%) and exhaled air (to be measured). The hypothesis of greater blood flow will be tested noninvasively by quantifying blood flow in the lungs and in the forearm. The anticipated outcome is a positive association between exhaled nitric oxide and oxygen extraction, pulmonary blood flow, forearm blood flow at rest and in response to exercise and in response to breathing 50% oxygen (without the stress of hypoxia). These findings would indicate that Tibetan highlanders use elevated nitric oxide in the lungs to offset high-altitude hypoxia and to deliver adequate oxygen to body tissues. Pulmonary nitric oxide appears central to understanding human adaptation to high altitude and hypoxia. Nitric oxide biology has implications for explaining how Tibetan high-altitude natives can achieve sea-level values for necessary biological processes that require oxygen, such as basal metabolism and physical work capacity, although they live in an environment where ambient oxygen is severely limited relative to sea level. The Tibetan case contributes to basic knowledge of nitric oxide biology because healthy people produce amounts that would be considered pathological at sea level. The proposed research contributes new knowledge to a central question in physical anthropology: the causes and consequences of human biological variation. The significance of the proposed research lies in improving understanding of how people adjust to life with hypoxia. It directly investigates why the Tibetan population inhabiting a stressful, high-altitude environment has very distinctive biological features and also has implications for understanding the responses of sea-level visitors to altitude whether they are vacationers in the Rockies or military personnel serving in mountainous areas, and for understanding the pathophysiology of patients with diseases that cause hypoxia .

该项目将研究一种新提出的机制，使人类能够适应极端环境中的生活。 藏人在高海拔地区生活了数千年，已被证明拥有多种适应青藏高原和喜马拉雅山脉生活的能力。 这项研究的目的是检验这样一个假设：藏族高原居民呼出的高浓度一氧化氮是一种提高其环境功能的反应，因为他们的环境中每次呼吸的氧分子较少，这种情况称为高原缺氧。 根据一氧化氮的已知作用，推测肺部高水平的一氧化氮有两个作用。 首先，它可以通过提取吸入空气中更大比例的氧气来抵消高海拔缺氧。 其次，它可以通过增加全身的血流量来改善氧气输送。 最近发现，高海拔藏族人在海平面呼出的一氧化氮是海平面土著人的两倍多，这需要解释，因为大量证据预测，在缺氧条件下，一氧化氮的合成会减少，而不是增加。 在西藏和安第斯土著高海拔人群中一致发现高肺一氧化氮表明其具有适应性、有益的功能。 这些假设将以生活在海拔 4200 米（约 14,000 英尺）的西藏自治区 91 名高海拔居民为样本进行检验。研究参与者将是健康的、未怀孕的、不吸烟的、18-55岁的人。 将测量呼出气中一氧化氮的浓度，预计会有很大的变化范围，包括比海平面上发现的值高两到三倍的值。 将通过测量吸入空气（20.9%）和呼出空气（待测量）中氧气百分比的差异来检验更高氧气提取的假设。 将通过量化肺部和前臂的血流量来无创地测试更大血流量的假设。 预期结果是呼出一氧化氮与氧提取、肺血流量、静息时前臂血流量、运动响应和呼吸 50% 氧气响应（没有缺氧压力）之间呈正相关。 这些发现表明，西藏高地人利用肺部升高的一氧化氮来抵消高原缺氧，并向身体组织提供足够的氧气。 肺一氧化氮似乎对于了解人类对高海拔和缺氧的适应至关重要。 一氧化氮生物学对于解释西藏高海拔地区的居民如何能够在需要氧气的必要生物过程（例如基础代谢和体力劳动能力）中达到海平面值具有重要意义，尽管他们生活在相对于海平面而言环境氧气严重有限的环境中。 西藏的案例有助于了解一氧化氮生物学的基础知识，因为健康人产生的一氧化氮量在海平面上被认为是病态的。 这项研究为体质人类学的一个核心问题提供了新的知识：人类生物变异的原因和后果。 这项研究的意义在于增进对人们如何适应缺氧生活的理解。 它直接调查了为什么生活在压力大的高海拔环境中的藏族人群具有非常独特的生物学特征，并且对于了解海平面游客对海拔的反应（无论是落基山脉的度假者还是在山区服役的军人）以及了解缺氧疾病患者的病理生理学具有重要意义。