伊贝沙坦对高血压患者内皮舒张功能和自主神经活性的干预效应

目的探讨高血压病患者血管内皮功能与自主神经活性变化及其影响因素.方法采用24h动态心电图测定心率变异的时域指标,应用高分辨超声测定的肱动脉血管舒张功能,比较60例低-中危高血压病患者和20例健康对照者血管内皮舒张功能、心率变异和糖脂代谢的变化,观察不同的降压药物-利尿剂(吲哒帕胺)和血管紧张素Ⅱ受体拮抗剂(伊贝沙坦)的影响.结果高血压病患者存在内皮依赖性血管舒张失调和自主神经活性异常,表现为总的心率变异下降,24h平均心率轻度增加,代表迷走活性的指标-rMSSD和PNN50显著低于对照组,血流介导的肱动脉血管舒张功能显著下降;高血压病患者餐后的2 h胰岛素浓度和胰岛素/血糖比值显著高于对照组;伊贝沙坦和吲哒帕胺的降压幅度相似;伊贝沙坦治疗8周显著改善了高血压病患者的胰岛素抵抗,显著增加了内皮依赖性血管舒张,引起了心率变异的迷走活性(rMSSD)增加和24 h平均心率下降,而吲哒帕胺无类似作用.结论高血压病患者存在血管内皮依赖性的舒张功能失调,改善高血压患者的胰岛素抵抗和自主神经活性可能是伊贝沙坦的有益作用机制之一.

Effects of Irbesartan on endothelial function and autonomic nervous system activity of patients with essential hypertension

Objective To investigate the effects of Irbesartan on endothelial function and autonomic nervous system activity of patients with essential hypertension. Methods The endothelium dependent flow mediated dilatation (F-MD) and the endothelium independent nitroglycerin mediated dilatation (NTG-MD) were evaluated by the brachial ultrasound examination. Time-domain indices of heart rate variability (HRV) were measured by 24 h ambulatory electrocardiogram. The changes of blood lipoproteins, blood glucose, insulin levels, endothelial function and heart rate variability in 60 patients with mild-moderate essential hypertension and 20 healthy controls were compared, and the effects of different antihypertensive agents (AT1 receptor blocker and diuretic) for 8-week treatment were observed. Results Endothelial dysfunction and abnormal autonomic nervous activity were observed in patients with mild-moderate essential hypertension as follow: mildly decreased total HRV and mildly increased 24-hour average heart rate, significantly decreased parasympathetic tone-rMSSD and PNN50, obviously lowered endothelium dependent F-MD. The postprandial insulin level and insulin/glucose ratio of patients with hypertension was significantly higher than that of healthy controls. The decreased blood pressure level caused by AT1 receptor blocker (Irbesartan) and diuretic (Indapamide) was similar. Irbesartan for 8-week therapy resulted in a significant improvement of the endothelium dependent F-MD and insulin resistence, the increase of vagal nervous activity and the decrease of 24-hour average heart rate, but Indapamide presented no such effects. Conclusion This study suggested that patients with mild-moderate essential hypertension have significantly abnormal endothelial function and autonomic nervous activity, and the beneficial effect of Irbesartan is associated with an improvement of insulin resistence and heart rate variability, not with the decrease of blood pressure level.