Cerebral blood flow regulation during acute increases in blood pressure: Can cerebral sympathetic nervous activity act as a gatekeeper?

血压急性升高期间的脑血流调节：脑交感神经活动可以充当看门人吗？

• 批准号: RGPIN-2020-06206
• 负责人: Brassard, Patrice
• 金额: $ 2.4万
• 依托单位: Université Laval
• 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=718264
• 关键词: Cerebral; blood; flow; regulation; during

Research in sleeping lambs suggests that the sympathetic nervous activity (SNA) in the brain has the potential to act as a gatekeeper for the cerebral microcirculation during transient increases in arterial blood pressure. However, whether an elevation in cerebral SNA attenuates cerebral blood flow changes during transient increases in arterial blood pressure remains to be clearly determined in humans. In addition, arterial carbon dioxide and cerebral metabolism will often change in physiological conditions associated with transient increases in arterial blood pressure, which will in turn influence the sympathetic control of the brain circulation. These key cerebral blood flow determinants need to be taken into account to isolate the role of cerebral SNA on cerebral blood flow regulation when arterial blood pressure acutely increases. I propose to identify the role of cerebral SNA during transient increases in arterial blood pressure using a regional approach based on norepinephrine spillover. The overall aim of this research program is to examine the role of cerebral SNA in the regulation of cerebral blood flow during transient increases in arterial blood pressure. SPECIFIC AIM 1: To directly quantify the change in cerebral SNA without the influence of hypocapnia during transient increases in arterial blood pressure, we will measure brain norepinephrine spillover during unilateral isometric handgrip and double leg isometric extension, with end-tidal carbon dioxide partial pressure clamped at baseline value. Then, to examine whether cerebral SNA attenuates the change in cerebral blood flow during transient increases in arterial blood pressure, we will measure brain norepinephrine spillover while pharmacologically blocking sympathetic nerves activity during transient increases in arterial blood pressure using the above-mentioned models. SPECIFIC AIM 2: To examine whether cerebral metabolism attenuates the impact of cerebral SNA on the change in cerebral blood flow during transient increases in arterial blood pressure, we will measure brain norepinephrine spillover, cerebral blood flow and metabolism during infusion of alpha-1 adrenoceptor agonist phenylephrine at rest and during exercise of increasing intensity, with end-tidal carbon dioxide partial pressure clamped at baseline value. Although previous research suggested that global SNA has a gatekeeper role for the brain vessels during transient increases in arterial blood pressure, whether an elevation in cerebral SNA attenuates cerebral blood flow changes when arterial blood pressure acutely increases has not been clearly demonstrated in intact humans. This proposal is a key milestone towards the direct quantification and examination of the specific role of cerebral SNA on human brain blood flow during physiological conditions associated with transient elevations in arterial blood pressure.

对睡眠羔羊的研究表明，脑中的交感神经活动（SNA）有可能在动脉血压短暂升高期间充当脑微循环的看门人。然而，脑SNA的升高是否会减弱动脉血压短暂升高期间的脑血流变化仍有待于在人类中明确确定。 此外，动脉二氧化碳和脑代谢通常会在与动脉血压瞬时升高相关的生理条件下发生变化，这反过来会影响脑循环的交感神经控制。当动脉血压急剧升高时，需要考虑这些关键的脑血流决定因素，以分离脑SNA对脑血流调节的作用。 我建议使用基于去甲肾上腺素溢出的区域方法来确定动脉血压短暂升高期间脑SNA的作用。 本研究计划的总体目标是检查脑SNA在动脉血压短暂升高期间对脑血流的调节作用。 具体目标1：为了在动脉血压一过性升高期间直接量化脑SNA的变化而不受低碳酸血症的影响，我们将在单侧等长握力和双腿等长伸展期间测量脑去甲肾上腺素溢出，潮气末二氧化碳分压固定在基线值。然后，为了检查脑SNA是否减弱动脉血压瞬时升高期间脑血流量的变化，我们将使用上述模型在动脉血压瞬时升高期间测量脑去甲肾上腺素溢出，同时阻断交感神经活动。 具体目标2：为了检查脑代谢是否减弱脑SNA对动脉血压一过性升高期间脑血流量变化的影响，我们将在静息和增加强度的运动期间，在呼气末二氧化碳分压固定在基线值的情况下，测量α-1肾上腺素受体激动剂苯肾上腺素输注期间的脑去甲肾上腺素溢出、脑血流量和代谢。 虽然以前的研究表明，全球SNA有一个看门人的作用，脑血管在短暂的动脉血压升高，是否在脑SNA的升高减弱脑血流量变化时，动脉血压急剧上升，并没有明确证明在完整的人。该提案是直接量化和检查脑SNA在与动脉血压瞬时升高相关的生理条件下对人脑血流的特定作用的关键里程碑。