Müller D N, Fiebeler A, Park J K, Dechend R, Luft F C
HELIOS Klinikum-Berlin, Medical Faculty of the Charitè, Humboldt University of Berlin, Germany.
Clin Nephrol. 2003 Jul;60 Suppl 1:S2-12.
Angiotensin (Ang) II and endothelin (ET-1) can both be regulated by NF-kappaB. They are, to variable degrees, also capable of activating NF-kappaB and increase the expression of NF-kappaB-dependent genes. Ang II-related vascular effects are in part mediated by ET-1. Nitric oxide synthase inhibition facilitates Ang II-related effects, which can be inhibited both by AT1-receptor blockers and by endothelin system inhibitors. This state-of-affairs supports the notion that a combined therapeutic strategy of inhibiting Ang II and ET-1 generation or blocking their effects at the receptor level would be superior to either strategy alone. Animal studies are encouraging but not without conflicting results. Angiotensin-converting enzyme inhibitors and AT1-receptor blockers have a superb track record in experimental animal models and in a host of clinical studies. Selective and nonselective blockers of the ET-1 receptors are important research tools and are also undergoing clinical trials. Inhibitors of the endothelin-converting enzyme have been developed. The recent elucidation of the endothelin-converting enzyme's physical structure should facilitate the development of still more novel compounds to inhibit ET-1 generation. We have recently engendered supportive evidence in this regard.
血管紧张素（Ang）II和内皮素（ET-1）均可受核因子κB（NF-κB）调控。它们在不同程度上还能够激活NF-κB并增加NF-κB依赖性基因的表达。Ang II相关的血管效应部分由ET-1介导。一氧化氮合酶抑制可促进Ang II相关效应，而这可被AT1受体阻滞剂和内皮素系统抑制剂所抑制。这种情况支持这样一种观点，即抑制Ang II和ET-1生成或在受体水平阻断其效应的联合治疗策略优于单独使用任何一种策略。动物研究令人鼓舞，但并非没有相互矛盾的结果。血管紧张素转换酶抑制剂和AT1受体阻滞剂在实验动物模型和大量临床研究中都有出色的记录。ET-1受体的选择性和非选择性阻滞剂是重要的研究工具，也正在进行临床试验。已经开发出内皮素转换酶抑制剂。最近对内皮素转换酶物理结构的阐明应有助于开发更多新型化合物以抑制ET-1的生成。我们最近在这方面获得了支持性证据。
