Mullen M J, Kharbanda R K, Cross J, Donald A E, Taylor M, Vallance P, Deanfield J E, MacAllister R J
Vascular Physiology Unit, Institute of Child Health and the Centre for Clinical Pharmacology, University College London, London, UK.
Circ Res. 2001 Feb 2;88(2):145-51. doi: 10.1161/01.res.88.2.145.
Flow-mediated dilatation (FMD) of conduit arteries is dependent on an intact endothelium, although the mechanisms are not fully understood. Using high-resolution ultrasound, we examined the role of endothelial mediators in radial artery dilatation in response to transient (short period of reactive hyperemia) and sustained (prolonged period of reactive hyperemia, hand warming, or an incremental infusion of acetylcholine into the distal radial artery) hyperemia. After short episodes of reactive hyperemia, FMD was abolished by local infusion of the nitric oxide synthesis inhibitor N:(G)monomethyl-L-arginine (5.3+/-1.2% versus 0.7+/-0.7%, P:<0.001). In contrast, basal vessel diameter and dilatation after prolonged episodes of reactive hyperemia, hand warming, and distal infusion of acetylcholine were not attenuated by nitric oxide synthesis inhibition. Inhibition of cyclooxygenase or local autonomic nervous system blockade also had no effect on FMD. Patients with hypercholesterolemia exhibited reduced FMD in response to transient hyperemia, but the response to sustained hyperemia was normal. These data suggest heterogeneity of endothelial responses to blood flow that are dependent on the characteristics of the flow stimulus. Dilatation after brief episodes of hyperemia is mediated by release of nitric oxide, whereas dilatation during sustained hyperemia is unaffected by NO synthesis inhibition. Hypercholesterolemia seems to differentially affect these pathways with impairment of the nitric oxide-dependent pathway and preservation of non nitric oxide-mediated dilatation to sustained flow stimuli.
尽管具体机制尚未完全明确，但传导动脉的血流介导的血管舒张（FMD）依赖于完整的内皮。我们使用高分辨率超声，研究了内皮介质在桡动脉对短暂（短时间反应性充血）和持续（长时间反应性充血、手部加温或向桡动脉远端递增注入乙酰胆碱）充血反应中的作用。在短暂的反应性充血发作后，局部注入一氧化氮合成抑制剂N-（G）-单甲基-L-精氨酸可消除FMD（5.3±1.2%对0.7±0.7%，P<0.001）。相比之下，长时间反应性充血、手部加温及乙酰胆碱远端注入后的基础血管直径和血管舒张不受一氧化氮合成抑制的影响。抑制环氧化酶或局部自主神经系统阻断对FMD也无影响。高胆固醇血症患者对短暂充血的FMD反应降低，但对持续充血的反应正常。这些数据表明内皮对血流的反应存在异质性，这取决于血流刺激的特征。短暂充血发作后的血管舒张由一氧化氮释放介导，而持续充血期间的血管舒张不受一氧化氮合成抑制的影响。高胆固醇血症似乎以不同方式影响这些途径，损害一氧化氮依赖途径，而保留对持续血流刺激的非一氧化氮介导的血管舒张。
