Dahlöf B, Herlitz H, Aurell M, Hansson L
Department of Medicine, University of Göteborg, Ostra Hospital, Sweden.
Am J Hypertens. 1992 Dec;5(12 Pt 1):900-11. doi: 10.1093/ajh/5.12.900.
Our study attempted to evaluate the importance of changes in the circulating renin-angiotensin-aldosterone system (RAAS) and in hemodynamics in relation to observed changes in cardiovascular structure. We studied previously untreated men (n = 28) with essential nonmalignant hypertension and a supine casual diastolic blood pressure > 95 mm Hg on three to four separate (> 1-week interval) occasions measured in triplicate. We used intraarterial blood pressure, dye-dilution technique, plethysmography (hands), eye-ground photos, M-mode echocardiography, radio immunoassays, and multiple regression analysis. Patients were randomized to 6 months of double-blind treatment with either enalapril or hydrochlorothiazide, following 4 to 6 weeks on placebo. We found that enalapril blocked the plasma angiotensin converting enzyme (ACE) with a secondary increment in plasma renin activity (PRA) and reductions in angiotensin II (AII) and aldosterone. Blood pressure was lowered through a reduction in total peripheral resistance (TPR). Hydrochlorothiazide increased PRA, AII, and aldosterone, and lowered blood pressure mainly through a reduction in cardiac output. Enalapril was significantly more effective than hydrochlorothiazide in reversing structural changes in the retinal and hand vasculature as well as in the heart. A reduction in cardiac hypertrophy was seen even in the occasional enalapril-treated patient, in whom little or no reduction in blood pressure occurred. In the stepwise regression analyses, the changes in retinal and hand vascular structure were most strongly related to various changes in the RAAS, explaining 15 to 34% of the variance. For the changes in cardiac structure, the type of therapy (enalapril or hydrochlorothiazide) appeared to be the most important factor, explaining between 29 and 50% of the variance. The changes in cardiac structure were even more strongly related to changes in the RAAS for the enalapril treated patients and explained up to 55% of the variance in cardiac structure. It can be concluded that the reversal of structural vascular changes during antihypertensive therapy was more dependent on the blockade of the RAAS than on lowering of the blood pressure.
我们的研究试图评估循环肾素 - 血管紧张素 - 醛固酮系统（RAAS）的变化以及血流动力学变化与所观察到的心血管结构变化之间的关系。我们研究了28名未经治疗的原发性非恶性高血压男性患者，其仰卧位随机舒张压> 95 mmHg，在三到四个不同的（间隔> 1周）时间点进行测量，每次测量三次。我们使用了动脉内血压测量、染料稀释技术、体积描记法（手部）、眼底照片、M型超声心动图、放射免疫测定和多元回归分析。患者在服用安慰剂4至6周后，被随机分配接受依那普利或氢氯噻嗪6个月的双盲治疗。我们发现依那普利可阻断血浆血管紧张素转换酶（ACE），导致血浆肾素活性（PRA）继发性升高，同时降低血管紧张素II（AII）和醛固酮水平。血压通过降低总外周阻力（TPR）而降低。氢氯噻嗪可升高PRA、AII和醛固酮水平，主要通过降低心输出量来降低血压。在逆转视网膜和手部血管以及心脏的结构变化方面，依那普利比氢氯噻嗪显著更有效。即使在偶尔接受依那普利治疗但血压几乎没有降低的患者中，也观察到了心肌肥厚的减轻。在逐步回归分析中，视网膜和手部血管结构的变化与RAAS的各种变化最密切相关，解释了15%至34%的变异。对于心脏结构的变化，治疗类型（依那普利或氢氯噻嗪）似乎是最重要的因素，解释了29%至50%的变异。对于接受依那普利治疗的患者，心脏结构的变化与RAAS的变化甚至更密切相关，解释了高达55%的心脏结构变异。可以得出结论，降压治疗期间血管结构变化的逆转更多地依赖于RAAS的阻断，而不是血压的降低。
