Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin.
Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan.
Microcirculation. 2019 Apr;26(3):e12518. doi: 10.1111/micc.12518. Epub 2019 Jan 15.
This study sought to determine whether salt-induced ANG II suppression contributes to impaired CBF autoregulation.
Cerebral autoregulation was evaluated with LDF during graded reductions of blood pressure. Autoregulatory responses in rats fed HS (4% NaCl) diet vs LS (0.4% NaCl) diet were analyzed using linear regression analysis, model-free analysis, and a mechanistic theoretical model of blood flow through cerebral arterioles.
Autoregulation was intact in LS-fed animals as MAP was reduced via graded hemorrhage to approximately 50 mm Hg. Short-term (3 days) and chronic (4 weeks) HS diet impaired CBF autoregulation, as evidenced by progressive reductions of laser Doppler flux with arterial pressure reduction. Chronic low dose ANG II infusion (5 mg/kg/min, i.v.) restored CBF autoregulation between the pre-hemorrhage MAP and 50 mm Hg in rats fed short-term HS diet. Mechanistic-based model analysis showed a reduced myogenic response and reduced baseline VSM tone with short-term HS diet, which was restored by ANG II infusion.
Short-term and chronic HS diet lead to impaired autoregulation in the cerebral circulation, with salt-induced ANG II suppression as a major factor in the initiation of impaired CBF regulation.
本研究旨在确定盐诱导的 ANG II 抑制是否有助于受损的 CBF 自动调节。
通过 LDF 在血压逐渐降低期间评估脑自动调节。使用线性回归分析、无模型分析以及脑小动脉血流的理论机制模型分析 HS(4%NaCl)饮食和 LS(0.4%NaCl)饮食喂养大鼠的自动调节反应。
LS 喂养的动物自动调节完好,因为通过分级放血将 MAP 降低至约 50mmHg。短期(3 天)和慢性(4 周)HS 饮食损害了 CBF 自动调节,这表现为随着动脉压降低,激光多普勒通量逐渐减少。慢性低剂量 ANG II 输注(5mg/kg/min,iv)可恢复短期 HS 饮食喂养大鼠的 CBF 自动调节,使其在预出血 MAP 和 50mmHg 之间恢复。基于机制的模型分析表明,短期 HS 饮食导致肌源性反应降低和基础 VSM 张力降低,而 ANG II 输注可恢复这一反应。
短期和慢性 HS 饮食导致脑循环自动调节受损,盐诱导的 ANG II 抑制是 CBF 调节受损的主要因素。