Orth S R, Viedt C, Amann K, Ritz E
Department of Internal Medicine, Ruperto Carola University, Heidelberg, Germany.
Intern Med. 2001 Apr;40(4):285-91. doi: 10.2169/internalmedicine.40.285.
The pathogenetic mechanisms leading to progression of renal failure are only partly understood. Several studies in immune- and non-immune-mediated models of renal damage have recently implicated the endothelin (ET) system as a major player in these processes. In animal models, ET receptor antagonists have been shown to be highly effective in abrogating the progression of renal failure. Furthermore, cardiac structural alterations seen in hypertension and/or renal insufficiency, e.g. left ventricular hypertrophy, thickening of intramyocardial arterioles, and the increase in non-vascular interstitial tissue, are largely prevented by ET receptor antagonists. In this context it is of interest that these beneficial renal and cardiac effects are, at least in most studies, independent of systemic blood pressure. In addition to the specific pharmacological blockade of the renin-angiotensin system [ACE inhibitors, angiotensin II receptor (AT1) antagonists], blockade of ET receptors or ET converting enzyme (ECE) may be a new tool to interfere with progression of renal failure and cardiovascular remodeling in humans.
导致肾衰竭进展的发病机制仅得到部分理解。最近，在免疫介导和非免疫介导的肾损伤模型中的多项研究表明，内皮素（ET）系统在这些过程中起主要作用。在动物模型中，ET受体拮抗剂已被证明在消除肾衰竭进展方面非常有效。此外，ET受体拮抗剂在很大程度上预防了高血压和/或肾功能不全时出现的心脏结构改变，例如左心室肥厚、心肌内小动脉增厚以及非血管间质组织增加。在这种情况下，有趣的是，至少在大多数研究中，这些有益的肾脏和心脏作用与全身血压无关。除了对肾素 - 血管紧张素系统的特异性药理阻断作用[ACE抑制剂、血管紧张素II受体（AT1）拮抗剂]外，阻断ET受体或ET转换酶（ECE）可能是干预人类肾衰竭进展和心血管重塑的一种新工具。
