Gansevoort R T, de Zeeuw D, de Jong P E
Department of Medicine, State University Hospital, Groningen, The Netherlands.
Kidney Int. 1994 Mar;45(3):861-7. doi: 10.1038/ki.1994.113.
Angiotensin converting enzyme (ACE) inhibition causes specific renal effects, such as a rise in effective renal plasma flow, a fall in filtration fraction and a lowering of proteinuria. The mechanism of these renal effects is still debated. Recent animal studies suggest that non-angiotensin (Ang) II related actions of ACE inhibition, such as bradykinin accumulation, may have a role. We therefore investigated the effects of specific intervention in the renin-angiotensin system with the Ang II receptor antagonist losartan, and compared these effects to those obtained with ACE inhibition, as this comparison might resolve the question whether or not the effects of ACE inhibition are Ang II related. The effects of losartan and enalapril were studied in eleven patients with non-diabetic proteinuria and hypertension. The protocol consisted of seven periods, each lasting one month, in which patients received once daily placebo, 50 mg losartan, 100 mg losartan, placebo, 10 mg enalapril, 20 mg enalapril, and placebo, respectively. At the end of each study period proteinuria, blood pressure, and renal function were determined. On both doses of losartan and enalapril proteinuria and blood pressure fell, whereas ERPF increased and GFR remained stable. The fall in urinary protein excretion was similar for both drugs: 46.3% (28.3% to 63.1%) on 100 mg losartan versus 51.6% (37.0% to 69.2%) on 20 mg enalapril (expressed as Wilcoxon-based estimated median with 95% CI).(ABSTRACT TRUNCATED AT 250 WORDS)
血管紧张素转换酶（ACE）抑制会产生特定的肾脏效应，如有效肾血浆流量增加、滤过分数降低和蛋白尿减少。这些肾脏效应的机制仍存在争议。最近的动物研究表明，ACE抑制的非血管紧张素（Ang）II相关作用，如缓激肽蓄积，可能起了作用。因此，我们研究了使用Ang II受体拮抗剂氯沙坦对肾素-血管紧张素系统进行特异性干预的效果，并将这些效果与ACE抑制所获得的效果进行比较，因为这种比较可能会解决ACE抑制的效果是否与Ang II相关这一问题。在11例非糖尿病蛋白尿和高血压患者中研究了氯沙坦和依那普利的效果。方案包括7个阶段，每个阶段持续1个月，患者分别每日服用一次安慰剂、50 mg氯沙坦、100 mg氯沙坦、安慰剂、10 mg依那普利、20 mg依那普利和安慰剂。在每个研究阶段结束时测定蛋白尿、血压和肾功能。氯沙坦和依那普利的两种剂量均使蛋白尿和血压下降，而有效肾血浆流量增加，肾小球滤过率保持稳定。两种药物使尿蛋白排泄的下降相似：100 mg氯沙坦时为46.3%（28.3%至63.1%），20 mg依那普利时为51.6%（37.0%至69.2%）（表示为基于威尔科克森法估计的中位数及95%置信区间）。（摘要截断于250字）
