Influence of peripheral chemoreceptors and hypoxia on neurovascular regulation and plasticity

外周化学感受器和缺氧对神经血管调节和可塑性的影响

• 批准号: RGPIN-2020-05385
• 负责人: Steinback, Craig
• 金额: $ 3.42万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=717612
• 关键词: Influence; peripheral; chemoreceptors; hypoxia; neurovascular

In the last 6 years I have made significant progress towards understanding the influence of hypoxia on cardiovascular function. This includes training a team of enthusiastic and successful HQP (n=42); the majority of whom have transitioned to skilled positions within their fields. Together we have published highly novel and impactful manuscripts, and made technological advances related to Natural Sciences and Engineering (NSE). This grant sets an exciting direction of research for the next 5yrs. Oxygen is critical for life and lack of sufficient oxygen (hypoxia) is met with significant corrective and compensatory physiological responses. I hypothesize that during hypoxia, the autonomic nervous system (via the sympathetic and parasympathetic systems) is a critical component of the compensatory cardiovascular response. I have laid out 3 related themes of research which address my hypothesis by advancing our understanding of the regulatory mechanism linking the autonomic nervous system to cardiovascular responses during hypoxia. Theme 1 will define how sympathetic neurons are activated and fire during hypoxia using direct neural recordings (microneurography) and advanced custom analysis software. We will directly link this activity to the amount and type of neurotransmitters released by these neurons using biochemical techniques. Finally, we will quantify the responsiveness of blood vessels to this chemical signaling using pharmacological agonists and antagonists. Theme 2 will identify the effects of parasympathetic nervous system signaling on the heart during hypoxia. We will use apnea and pharmacological antagonists as a potent tools to unmask the effects of the parasympathetic system during hypoxia. The time-course of influence on cardiac rate and rhythm during prolonged periods of hypoxia (hours to months) will be assessed during wakefulness and sleep. Theme 3 is comprised of 3 research expeditions to define the adaptive phenotypes of the world's high-altitude populations. This is a direct extension of our previous work in Nepal and Peru. We will capture the first data on neuro-cardiovascular control in high-altitude Ethiopians, who have resided at altitude the longest (>70,000yrs). We will contrast this data with high-altitude North American's who migrated to altitude regions only 200yrs ago. These individuals are also the perfect contrast to our acclimatization work in North American Low-landers. Finally, we will return to Nepal to fill a huge gap related to high-lander and low-lander female cardiovascular control during hypoxia. All research will be led by HQP, who will gain significant technical and theoretical training to prepare them as the next leaders in NSE. The findings from this line of research will be directly relevant to the >200million people living at altitude, the millions of people that travel to altitude for work or recreation, and translated to medical research in patients with respiratory or cardiovascular disease.

在过去的6年里，我在了解缺氧对心血管功能的影响方面取得了重大进展。这包括培训一个充满热情和成功的HQP团队（n=42）；他们中的大多数人已经在各自的领域内过渡到技术岗位。我们一起发表了非常新颖和有影响力的手稿，并取得了与自然科学和工程（NSE）相关的技术进步。这笔拨款为今后5年的研究确定了一个令人兴奋的方向。