Harris R C, Martinez-Maldonado M
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tenn 37232-2372, USA.
Miner Electrolyte Metab. 1995;21(4-5):328-35.
During the past decade, experimental and clinical evidence has indicated an important role for the renin-angiotensin system in the progressive destruction of nephrons in a wide variety of chronic renal diseases. Studies have indicated that in the subtotally nephrectomized rat model of progressive glomerulosclerosis, in experimental diabetes mellitus, in the chronic phase of puromycin aminonucleoside-induced nephrotic syndrome and in Heymann's nephritis, angiotensin-converting enzyme (ACE) inhibitors dramatically preserve both nephron structure and function. Clinical studies have similarly noted that chronic administration of ACE inhibitors inhibits progression of renal failure in type I diabetes and type II diabetes as well as primary glomerulopathies, sickle cell nephropathy, systemic lupus erythematosis, chronic pyelonephritis and adult polycystic kidney disease. Current evidence suggests that the beneficial effect of ACE inhibitors is primarily due to inhibition of angiotensin II production, and there is strong suggestive evidence for increases in local intrarenal activation of the renin-angiotensin system in these conditions. In obstructive uropathy, activation of the renin-angiotensin system has also been shown to be an important aspect of the early functional changes and may be of importance in the subsequent generation of interstitial fibrosis. In the obstructed kidney, renin and angiotensinogen production increase and type I angiotensin receptors decrease. Inhibitors of angiotensin II production and angiotensin II action partially reverse the vasoconstriction and the reduced renal blood flow, and abolish the changes in expression of AT1 MRNA induced by obstruction. Studies suggest that the angiotensin-mediated increases in tubulointerstitial fibrosis may be mediated by increased production of transforming growth factor-beta.
在过去十年中，实验和临床证据表明肾素 - 血管紧张素系统在多种慢性肾脏疾病的肾单位进行性破坏中起重要作用。研究表明，在渐进性肾小球硬化的次全肾切除大鼠模型、实验性糖尿病、嘌呤霉素氨基核苷诱导的肾病综合征慢性期以及海曼肾炎中，血管紧张素转换酶（ACE）抑制剂能显著保护肾单位结构和功能。临床研究同样指出，长期使用ACE抑制剂可抑制I型糖尿病、II型糖尿病以及原发性肾小球病、镰状细胞肾病、系统性红斑狼疮、慢性肾盂肾炎和成人多囊肾病中肾衰竭的进展。目前的证据表明，ACE抑制剂的有益作用主要归因于对血管紧张素II生成的抑制，并且有强有力的提示性证据表明在这些情况下肾内肾素 - 血管紧张素系统的局部激活增加。在梗阻性尿路病中，肾素 - 血管紧张素系统的激活也已被证明是早期功能变化的一个重要方面，并且可能在随后的间质纤维化形成中起重要作用。在梗阻的肾脏中，肾素和血管紧张素原的产生增加，I型血管紧张素受体减少。血管紧张素II生成抑制剂和血管紧张素II作用抑制剂可部分逆转血管收缩和肾血流量减少，并消除梗阻诱导的AT1 mRNA表达变化。研究表明，血管紧张素介导的肾小管间质纤维化增加可能由转化生长因子 - β产生增加介导。
