Department of Medicine, Division of Nephrology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
J Renin Angiotensin Aldosterone Syst. 2010 Mar;11(1):37-41. doi: 10.1177/1470320309347787. Epub 2009 Oct 27.
Suppression of angiotensin II formation by angiotensin-converting enzyme inhibitors or blockade of the angiotensin II receptor by angiotensin receptor blockers is a powerful therapeutic strategy to slow the progression of renal disease. However, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers provide only imperfect protection against the progression of chronic kidney disease to end-stage renal failure. Hence, innovative approaches are needed to keep patients with chronic kidney disease off dialysis. Angiotensin II activates at least two receptors, namely the angiotensin II type 1 (AT( 1)) and angiotensin II type 2 (AT(2)) receptors. The majority of the effects of angiotensin II, such as vasoconstriction, inflammation, and matrix deposition, are mediated via the AT(1) receptor. It is thought that the AT(2) receptor counteracts these effects and plays a role in nephroprotection. However, recent data support the notion that the AT(2) receptor transduces pro-inflammatory effects and promotes fibrosis and hypertrophy. Therefore, the question of whether stimulation of the AT(2) receptor could represent a silver bullet for the treatment of chronic kidney disease or may, on the contrary, exert detrimental effects on renal physiology remains unresolved. Recent data from AT(2) receptor-knockout mice demonstrate that the loss of AT(2) receptor signalling is associated with increased renal injury and mortality in chronic kidney disease. This raises the expectation that pharmacological stimulation of the AT(2) receptor may positively influence renal pathologies. However, further research is needed to explore the question whether AT(2) receptor stimulation may represent a new therapeutic strategy for the treatment of chronic kidney disease.
血管紧张素转化酶抑制剂抑制血管紧张素 II 的形成或血管紧张素受体阻断剂阻断血管紧张素 II 受体，是减缓肾脏疾病进展的强有力的治疗策略。然而，血管紧张素转化酶抑制剂和血管紧张素受体阻断剂仅能提供不完全的保护，防止慢性肾脏病进展为终末期肾衰竭。因此，需要创新的方法来使慢性肾脏病患者避免透析。血管紧张素 II 激活至少两种受体，即血管紧张素 II 型 1（AT（1））和血管紧张素 II 型 2（AT（2））受体。血管紧张素 II 的大多数作用，如血管收缩、炎症和基质沉积，都是通过 AT（1）受体介导的。人们认为 AT（2）受体对抗这些作用，并在肾脏保护中发挥作用。然而，最近的数据支持这样一种观点，即 AT（2）受体转导促炎作用，并促进纤维化和肥大。因此，刺激 AT（2）受体是否能成为治疗慢性肾脏病的银弹，或者相反，是否会对肾脏生理产生有害影响，这个问题仍然没有解决。来自 AT（2）受体敲除小鼠的最新数据表明，AT（2）受体信号的丧失与慢性肾脏病中肾脏损伤和死亡率的增加有关。这使得人们期望，AT（2）受体的药理学刺激可能对肾脏病理产生积极影响。然而，需要进一步的研究来探讨 AT（2）受体刺激是否可能成为治疗慢性肾脏病的新治疗策略。
