London G M, Pannier B, Vicaut E, Guérin A P, Marchais S J, Safar M E, Cuche J L
Centre Hospitalier F.H. Manhes, Fleury-Mérogis, France.
J Hypertens. 1996 Sep;14(9):1139-46. doi: 10.1097/00004872-199609000-00015.
To assess the respective roles of the anti-hypertensive and blood pressure-independent effects of angiotensin converting enzyme (ACE) inhibition in the changed arterial haemodynamics observed in hypertensive patients with end-stage renal disease (ESRD) treated by haemodialysis.
Twelve hypertensive patients with ESRD were included in a double-blind, cross-over study comparing a single 20 mg dose of the ACE inhibitor quinapril versus placebo. Two study periods each of 172 h duration were separated by a 2-week placebo period. Repeated measurements of the following parameters were performed: brachial artery systolic blood pressure (SBP); diastolic blood pressure and mean blood pressure (using a mercury sphygmomanometer); carotid artery SBP and pulse pressure (by applanation tonometry); aortic stiffness (by pulse wave velocity); and the effect of arterial wave reflections in the common carotid artery (the augmentation index, by applanation tonometry). A radioimmunoassay was used to determine plasma angiotensin II levels. Quinaprilat pharmacokinetics were studied using a specific assay. Two-way (time-treatment) analysis of variance for repeated measures, analysis of covariance for two within-factors and a covariate changing with the level of the factor time (pressures measured at each time) and baseline values of the studied parameter as a second covariate were used for statistical analysis.
Quinapril treatment induced a long-lasting decrease in arterial wave reflections, which was still observable 172 h after quinapril administration and still present after removing the effect of the decrease in blood pressure. The effect on wave reflections was associated with a more pronounced and sustained decrease in carotid SBP and pulse pressure than that in brachial SBP and pulse pressure. Quinapril administration also induced a long-lasting decrease in aortic pulse wave velocity, but this effect was entirely dependent on parallel changes in blood pressure. Arterial haemodynamic changes were not related to plasma angiotensin II or quinaprilat levels.
The results of this controlled study indicate that, in ESRD patients, ACE inhibition results in a long-lasting, blood pressure-independent decrease in arterial wave reflections. The consequence of this was a decrease in pulsatile pressure load in the central arteries with increased aortic distensibility. The increased aortic distensibility resulted from the decrease in blood pressure. The observed arterial haemodynamic alterations suggest that ACE inhibition induced alterations in arterial wave reflections in the distal parts of the arterial tree.
评估血管紧张素转换酶（ACE）抑制在接受血液透析治疗的终末期肾病（ESRD）高血压患者中所观察到的动脉血流动力学变化中，降压作用及血压非依赖性作用各自所起的作用。
12例ESRD高血压患者纳入一项双盲交叉研究，比较单次20mg剂量的ACE抑制剂喹那普利与安慰剂。两个为期172小时的研究期之间间隔2周的安慰剂期。对以下参数进行重复测量：肱动脉收缩压（SBP）；舒张压和平均血压（使用汞柱式血压计）；颈动脉SBP和脉压（采用压平式眼压计）；主动脉僵硬度（通过脉搏波速度）；以及颈总动脉中动脉波反射的影响（增强指数，采用压平式眼压计）。采用放射免疫分析法测定血浆血管紧张素II水平。使用特定检测方法研究喹那普利拉的药代动力学。采用重复测量的双向（时间-治疗）方差分析、两个组内因素的协方差分析以及随因素时间水平变化的协变量（每次测量的血压）和研究参数的基线值作为第二个协变量进行统计分析。
喹那普利治疗导致动脉波反射持续降低，在给予喹那普利172小时后仍可观察到，且在去除血压降低的影响后依然存在。对波反射的影响与颈动脉SBP和脉压相比肱动脉SBP和脉压更显著且持续的降低相关。给予喹那普利还导致主动脉脉搏波速度持续降低，但这种作用完全依赖于血压的平行变化。动脉血流动力学变化与血浆血管紧张素II或喹那普利拉水平无关。
这项对照研究的结果表明，在ESRD患者中，ACE抑制导致动脉波反射出现持续的、血压非依赖性降低。其结果是中心动脉搏动压力负荷降低，主动脉扩张性增加。主动脉扩张性增加是由血压降低所致。观察到的动脉血流动力学改变提示，ACE抑制引起动脉树远端部分的动脉波反射改变。
