Dover Anna R, Hadoke Patrick W F, Walker Brian R, Newby David E
Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, Scotland, UK.
J Cardiovasc Pharmacol. 2007 Sep;50(3):321-6. doi: 10.1097/FJC.0b013e3180cab148.
Acute coronary events occur most commonly in the morning, when circadian variations dictate that endogenous fibrinolytic activity is low and cortisol levels are high. We hypothesized that glucocorticoids would impair the acute fibrinolytic capacity of the endothelium because chronic glucocorticoid excess is associated with a prothrombotic state and endothelial vasomotor dysfunction. Twelve healthy subjects attended on 3 occasions and received oral metyrapone followed by intravenous saline or low-dose or high-dose hydrocortisone. Forearm blood flow and fibrinolytic indices were measured using venous occlusion plethysmography during intrabrachial bradykinin, acetylcholine, and sodium nitroprusside infusion. Hydrocortisone infusion had no effect on systemic concentrations of plasminogen activator inhibitor type 1 (PAI-1) or tissue plasminogen activator (t-PA; P = 0.10 and 0.95, respectively). Bradykinin caused a dose-dependent increase in plasma t-PA concentrations (P < 0.0001) that was unaffected by systemic hydrocortisone administration. Intrabrachial infusions of bradykinin, acetylcholine, and sodium nitroprusside all caused dose-dependent increases in forearm blood flow (P < 0.05) that were unaltered by hydrocortisone infusions.Short-term variations in plasma cortisol concentrations within the physiological range do not affect endothelial fibrinolytic or vasomotor function in healthy volunteers. These findings suggest that glucocorticoids do not exert acute effects on endothelial function in vivo in humans.
急性冠脉事件最常发生在早晨，此时昼夜节律变化表明内源性纤溶活性较低而皮质醇水平较高。我们推测，糖皮质激素会损害内皮的急性纤溶能力，因为长期糖皮质激素过量与血栓形成前状态和内皮血管舒缩功能障碍有关。12名健康受试者分3次前来，先口服甲吡酮，随后静脉输注生理盐水或低剂量或高剂量氢化可的松。在肱动脉内输注缓激肽、乙酰胆碱和硝普钠期间，使用静脉阻塞体积描记法测量前臂血流量和纤溶指标。输注氢化可的松对1型纤溶酶原激活物抑制剂（PAI-1）或组织纤溶酶原激活物（t-PA）的全身浓度没有影响（P分别为0.10和0.95）。缓激肽使血浆t-PA浓度呈剂量依赖性增加（P<0.0001），全身给予氢化可的松对此无影响。肱动脉内输注缓激肽、乙酰胆碱和硝普钠均使前臂血流量呈剂量依赖性增加（P<0.05），输注氢化可的松未改变这种情况。生理范围内血浆皮质醇浓度的短期变化不会影响健康志愿者的内皮纤溶或血管舒缩功能。这些发现表明，糖皮质激素在人体内对内皮功能没有急性影响。
