Department of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada.
J Hypertens. 2012 Apr;30(4):725-33. doi: 10.1097/HJH.0b013e32835050ca.
AMP-activated protein kinase (AMPK) activity may alter blood pressure by directly influencing vascular tone. The purpose of this study is to examine if these effects occur acutely in a model of hypertension.
Using distinct groups of Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) we compare baseline aortic and mesenteric artery AMPK activation (by immunoblotting), hemodynamic (blood pressure and heart rate via carotid catheter) and biochemical responses to an acute injection of AMPK activator 5-aminoimidazole-4-carboxyamide-1-β-D-ribofuranoside (AICAR) in vivo and vasomotor responses of isolated mesenteric vessels to AICAR exposure in vitro using myography. Mean arterial pressure (MAP) decreased from 196 ± 3 to 122 ± 15 mmHg (P < 0.001) during the 30 min following AICAR injection in SHR (an effect partially prevented by NOS inhibitor L-NAME), but in WKY MAP was unaffected by AICAR. Basal AMPK activation (phosphorylation of AMPK activation site threonine 172) was reduced by approximately 50% in aorta of SHR vs. WKY (0.49 ± 0.1 vs. 1.0 ± 0.1 arbitrary units, P < 0.001), and was improved approximately 1.6-fold in SHR but not in WKY aorta 30 min following AICAR injection. In isolated vessel experiments, dose-dependent vasorelaxation to AICAR was similar in mesenteric arteries of SHR and WKY, although responses were more reliant on nitric oxide in SHR vs. WKY.
The ability of AICAR to improve vascular AMPK activation, and to generate parallel reductions in blood pressure and relaxation of SHR resistance vasculature, highlights the potential importance of AMPK in the regulation of blood pressure and vascular tone.
AMP 激活的蛋白激酶（AMPK）活性可通过直接影响血管张力来改变血压。本研究旨在检查在高血压模型中这些作用是否会急性发生。
使用不同组别的 Wistar-Kyoto 大鼠（WKY）和自发性高血压大鼠（SHR），我们比较了主动脉和肠系膜动脉 AMPK 激活（通过免疫印迹）、血流动力学（颈动脉导管测量血压和心率）以及急性注射 AMPK 激活剂 5-氨基咪唑-4-甲酰胺-1-β-D-核糖呋喃糖苷（AICAR）时的生化反应，以及在体内心血管系统对 AICAR 暴露的血管舒缩反应，使用离体肠系膜血管的肌电图。在 SHR 中，AICAR 注射后 30 分钟内，平均动脉压（MAP）从 196±3mmHg 降至 122±15mmHg（P<0.001）（这一作用部分被一氧化氮合酶抑制剂 L-NAME 所阻止），但在 WKY 中，MAP 不受 AICAR 影响。与 WKY 相比，SHR 主动脉中的 AMPK 激活（AMPK 激活位点苏氨酸 172 的磷酸化）降低了约 50%（0.49±0.1 对 1.0±0.1 任意单位，P<0.001），并且在 AICAR 注射 30 分钟后，SHR 但不是 WKY 的主动脉 AMPK 激活增加了约 1.6 倍。在离体血管实验中，AICAR 引起的肠系膜动脉剂量依赖性舒张反应在 SHR 和 WKY 中相似，尽管 SHR 中的反应更依赖于一氧化氮，而不是 WKY。
AICAR 改善血管 AMPK 激活的能力，以及平行降低 SHR 阻力血管的血压和舒张，突显了 AMPK 在调节血压和血管张力方面的潜在重要性。
