Joannides Robinson, Bellien Jeremy, Thurlure Celine, Iacob Michele, Abeel Murielle, Thuillez Christian
Department of Pharmacology, Rouen University Hospital & INSERM U644 (IFRMP 23), Institute for Biomedical Research, University of Rouen, Rouen Cedex, France.
Am J Hypertens. 2008 Jun;21(6):679-84. doi: 10.1038/ajh.2008.39. Epub 2008 Apr 3.
Fixed combination of angiotensin-converting enzyme inhibitors (ACEIs) with thiazide-type diuretics at low dose has been used as first-line therapy for the treatment of essential hypertension but their effect on conduit artery endothelial dysfunction remains unknown.
Thirteen hypertensive patients were assessed after acute administration of a placebo, fixed combination of perindopril-indapamide at low dose: D1 (2 mg/0.625 mg) and twice this dose: D2 (4 mg/1.25 mg), during a double-blind, randomized, crossover study, and were compared with 13 matched controls. Mean arterial pressure (MAP), radial artery diameter (echotracking) and flow (Doppler) were measured during flow-mediated dilatation (FMD) induced by post-ischemic hyperemia (PIH). PIH was characterized by peak flow and duration of hyperemia (t(1/2)). Endothelium-independent dilatation was assessed by trinitrine.
In hypertensive patients compared with controls, basal radial artery diameter and flow, peak flow, and trinitrine responses were similar while MAP was increased (115 +/- 3 vs. 87 +/- 2 mm Hg), t(1/2) was decreased (11.1 +/- 1.9 vs. 17.2 +/- 2.2 s), and FMD was altered (radial diameter increase: 203 +/- 14 vs. 304 +/- 15 microm). Compared with placebo, only D2 decreased MAP (placebo: 115 +/- 3; D1: 112 +/- 4; D2: 103 +/- 4 mm Hg) and increased t(1/2) (placebo: 11.1 +/- 1.9; D1: 8.7 +/- 1.5; D2:13.0 +/- 1.9 s). Conversely, D1 and D2 increased FMD (placebo: 203 +/- 14; D1: 218 +/- 22; D2: 227 +/- 23 microm) with no change in basal diameter and flow, peak flow, and trinitrine responses.
These results demonstrate that a fixed combination of ACEI/diuretic at low dose significantly improves radial artery FMD in hypertensive patients and suggest a direct effect on conduit artery endothelium that may contribute to vascular protection.
血管紧张素转换酶抑制剂（ACEIs）与低剂量噻嗪类利尿剂的固定组合已被用作治疗原发性高血压的一线疗法，但其对传导动脉内皮功能障碍的影响尚不清楚。
在一项双盲、随机、交叉研究中，对13例高血压患者在急性给予安慰剂、低剂量培哚普利 - 吲达帕胺固定组合：D1（2毫克/0.625毫克）和该剂量两倍：D2（4毫克/1.25毫克）后进行评估，并与13例匹配的对照者进行比较。在缺血后充血（PIH）诱导的血流介导的血管舒张（FMD）过程中测量平均动脉压（MAP）、桡动脉直径（回声跟踪）和血流（多普勒）。PIH的特征为血流峰值和充血持续时间（t(1/2)）。通过硝酸甘油评估非内皮依赖性血管舒张。
与对照者相比，高血压患者的基础桡动脉直径和血流、血流峰值以及硝酸甘油反应相似，而MAP升高（115±3对87±2毫米汞柱），t(1/2)降低（11.1±1.9对17.2±2.2秒），且FMD改变（桡动脉直径增加：203±14对304±15微米）。与安慰剂相比，只有D2降低了MAP（安慰剂：115±3；D1：112±4；D2：103±4毫米汞柱）并增加了t(1/2)（安慰剂：11.1±1.9；D1：8.7±1.5；D2：13.0±1.9秒）。相反，D1和D2增加了FMD（安慰剂：203±14；D1：218±22；D2：227±23微米），而基础直径和血流、血流峰值以及硝酸甘油反应无变化。
这些结果表明，低剂量的ACEI/利尿剂固定组合可显著改善高血压患者的桡动脉FMD，并提示对传导动脉内皮有直接作用，这可能有助于血管保护。
