Blezer E L, Nicolay K, Bär D, Goldschmeding R, Jansen G H, Koomans H A, Joles J A
Department of Nephrology, University Hospital Utrecht, Netherlands.
Stroke. 1998 Aug;29(8):1671-7; discussion 1677-8. doi: 10.1161/01.str.29.8.1671.
Stroke-prone spontaneously hypertensive rats (SHRSP), subjected to high NaCl intake, show severe hypertension, organ damage, and early death. Preventive treatment with an angiotensin-converting enzyme (ACE) inhibitor is known to reduce mortality. Previously we found that proteinuria always precedes cerebral edema in SHRSP. Hence, in this study ACE inhibition was started later, ie, directly after manifestation of either proteinuria or cerebral edema.
SHRSP were subjected to 1% NaCl intake. Group 1 served as a control. In group 2 early-onset treatment with the ACE inhibitor enalapril was initiated after proteinuria was >40 mg/d. In group 3 late-onset ACE inhibition was started after the first observation of cerebral edema with T2-weighted MRI. Cerebral edema was expressed as the percentage of pixels with an intensity above a defined threshold.
In controls median survival was 54 days (range, 32 to 80 days) after start of salt loading. The terminal level of cerebral edema was 19.0+/-3.0%. Under early-onset enalapril, median survival increased to 320 days (range, 134 to 368 days; P<0.01 versus group 1). Cerebral edema was prevented in all but 1 rat. Systolic blood pressure was slightly and transiently reduced at day 14. Proteinuria was markedly reduced (52+/-7 versus 190+/-46 mg/d in group 1 at day 7; P<0.05). Under late-onset enalapril, median survival was 264 days (range, 154 to 319 days; P<0.01 versus group 1). Cerebral edema decreased to baseline levels (9.6+/-2.9 at day 0 to 3.4+/-0.5% at day 3; (P<0.05). Ultimately cerebral edema reoccurred in 6 of the 8 rats. SBP decreased slightly at day 7 only. Proteinuria decreased from 283+/-27 at day 0 to 116+/-22 mg/d at day 7 (P<0.05). Complete remission of the original locus of cerebral edema was confirmed histologically.
In SHRSP with proteinuria, treatment with an ACE inhibitor both prevented the development of cerebral edema and reduced manifest cerebral edema and proteinuria. Survival was markedly prolonged. These findings support the use of ACE inhibition for treatment in hypertensive encephalopathy.
易患中风的自发性高血压大鼠（SHRSP），给予高盐饮食后，会出现严重高血压、器官损伤及早期死亡。已知用血管紧张素转换酶（ACE）抑制剂进行预防性治疗可降低死亡率。此前我们发现，在SHRSP中蛋白尿总是先于脑水肿出现。因此，在本研究中，ACE抑制治疗开始得较晚，即蛋白尿或脑水肿出现后立即开始。
对SHRSP给予1%的盐饮食。第1组作为对照。第2组在蛋白尿>40mg/d后开始用ACE抑制剂依那普利进行早期治疗。第3组在首次通过T2加权磁共振成像观察到脑水肿后开始进行晚期ACE抑制治疗。脑水肿以强度高于定义阈值的像素百分比表示。
在对照组中，开始高盐饮食后中位生存期为54天（范围32至80天）。脑水肿的终末水平为19.0±3.0%。在早期给予依那普利治疗时，中位生存期延长至320天（范围134至368天；与第1组相比，P<0.01）。除1只大鼠外，所有大鼠的脑水肿均得到预防。收缩压在第14天有轻微短暂下降。蛋白尿显著减少（第7天时，第2组为52±7mg/d，第1组为190±46mg/d；P<0.05）。在晚期给予依那普利治疗时，中位生存期为264天（范围154至319天；与第1组相比，P<0.01）。脑水肿降至基线水平（第0天时为9.6±2.
