The cardiac-sympathetic contribution to blood pressure regulation

心脏交感神经对血压调节的贡献

• 批准号: RGPIN-2020-06240
• 负责人: West, Christopher
• 金额: $ 2.77万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=741111
• 关键词: cardiac; sympathetic; contribution; blood; pressure

The arterial baroreflex is arguably one of the most important reflexes in the control of arterial blood pressure (BP). The baroreflex buffers acute fluctuations in BP that occur during physiological stressors by controlling cardiac output and total peripheral resistance. Thus the `output' from the baroreflex is considered to consist of a heart rate (cardiopulmonary arm) and vascular component (sympathetic arm). In conducting integrative physiological studies in rodents with spinal transection over the last 5-8 years, my lab has made a number of key observations that imply there may also be a cardiac inotropic (i.e., cardiac-sympathetic) arm to the arterial baroroeflex. Recently, we have found that when the arterial baroreceptors are unloaded there is not only an increase in peripheral vascular resistance and heart rate but there is also an increase in cardiac inotropic function. Though such a response is logical, direct evidence supporting the presence of a cardiac-inotropic arm to the arterial baroreflex control of blood pressure is lacking. Moreover, fundamental shortcomings exist in our understanding of the neuroanatomical pathways that are important in transducing this response from the brainstem to the heart and blood vessels. Over the next 5 years we will comprehensively study the presence of a functional cardiac-inotropic arm to the baroreflex along with the underlying neuroanatomic pathways that control this response, with a particular emphasis on spinal segmental control. We will specifically assess whether mechanical and pharmacological manipulation of the baroreflex results in similar cardiac and vascular outputs, as well as testing whether control mechanisms differ by sex and are impacted by activation of the chemoreflex. We will also continue our ongoing efforts to modify the post-processing software available for human sympathetic recordings to study and decode sympathetic neural transmission in rodents, wherein we will additionally relate such strategies to end-organ function. Establishing and validating the presence of a functional cardiac-inotropic arm to the baroreflex and determining the underlying neuroanatomical control is expected to advance our basic understanding of how the baroreflex functions to maintain arterial blood pressure. The studies proposed span a number of diverse fields and provide an excellent training environment for HQP who will be trained in all aspects of the surgical preparation and advanced data processing.

动脉压力感受性反射是控制动脉血压的重要反射之一。压力反射通过控制心输出量和总外周阻力来缓冲生理应激期间发生的BP的急性波动。因此，压力感受器反射的“输出”被认为是由心率（心肺臂）和血管成分（交感臂）组成。在过去的5-8年里，在对脊髓横断的啮齿动物进行综合生理学研究时，我的实验室进行了一些关键的观察，这些观察表明也可能存在心脏变力性（即，心脏交感神经）臂到动脉压力反射。 最近，我们发现当动脉压力感受器卸载时，不仅外周血管阻力和心率增加，而且心脏变力功能也增加。虽然这样的反应是合乎逻辑的，直接的证据支持的存在心脏变力臂动脉压力反射控制血压是缺乏的。此外，我们对神经解剖学通路的理解存在根本性的缺陷，而神经解剖学通路在将这种反应从脑干传导到心脏和血管方面很重要。 在接下来的5年里，我们将全面研究压力反射的功能性心脏变力臂的存在，沿着控制这种反应的潜在神经解剖学通路，特别强调脊髓节段控制。我们将专门评估压力反射的机械和药理学操作是否会导致类似的心脏和血管输出，以及测试控制机制是否因性别而异，并受到化学反射激活的影响。我们还将继续我们正在进行的努力，以修改后处理软件可用于人类交感神经记录研究和解码啮齿动物的交感神经传递，其中我们将另外将这些策略与终末器官功能联系起来。建立和验证压力反射的功能性心脏变力臂的存在，并确定潜在的神经解剖控制，预计将推进我们对压力反射如何维持动脉血压的基本理解。所提出的研究跨越了许多不同的领域，并为HQP提供了一个极好的培训环境，HQP将接受手术准备和高级数据处理的所有方面的培训。