Peluso Antonio A B, Santos Robson A S, Unger Thomas, Steckelings U Muscha
aDepartment of Cardiovascular and Renal Research, Institute for Molecular Medicine, University of Southern Denmark, Odense, Denmark bNational Institute of Science and Technology in Nanobiopharmaceutics, Belo Horizonte, Brazil cCARIM, Maastricht University, Maastricht, The Netherlands.
Curr Opin Nephrol Hypertens. 2017 Jan;26(1):36-42. doi: 10.1097/MNH.0000000000000289.
Angiotensin II is a main regulator of kidney function. Renal actions mediated by the angiotensin AT1 receptor have been well known for many years. In contrast, several details of angiotensin AT2 receptor actions in kidney physiology and pathophysiology were only described very recently. These findings are reviewed in this article.
Regarding the role of the angiotensin AT2 receptor in kidney physiology, a major recent finding was that the AT2 receptor-mediated inhibition of Na-H exchanger-3 and Na/K-ATPase in the renal proximal tubules is caused by internalisation of these transporters, thus reducing reabsorption and increasing natriuresis/diuresis. Regarding renal pathology, several studies demonstrated an attenuation of renal injury caused by diabetes or by obesity with or without high-salt diet through anti-inflammatory, antifibrotic, and antioxidative mechanisms. Generally, AT2 receptor expression seems increased and AT2 receptor-mediated effects stronger in female and obese animals.
The recent findings about the role of the angiotensin AT2 receptor in renal health and disease strongly suggest that pharmacological targeting of this receptor with selective agonists is a promising therapeutic strategy for inducing diuresis/natriuresis (also additive to established diuretics) and for the treatment of diabetic nephropathy or kidney disease of other pathogenesis.
血管紧张素II是肾功能的主要调节因子。血管紧张素AT1受体介导的肾脏作用多年来已为人熟知。相比之下,血管紧张素AT2受体在肾脏生理和病理生理中的作用细节直到最近才被描述。本文对这些发现进行综述。
关于血管紧张素AT2受体在肾脏生理中的作用,最近的一项主要发现是,AT2受体介导的对肾近端小管中钠氢交换体-3和钠钾ATP酶的抑制是由这些转运蛋白的内化引起的,从而减少重吸收并增加尿钠排泄/利尿。关于肾脏病理学,多项研究表明,通过抗炎、抗纤维化和抗氧化机制,糖尿病或肥胖(无论是否高盐饮食)所致的肾损伤会减轻。一般来说,在雌性和肥胖动物中,AT2受体表达似乎增加,且AT2受体介导的效应更强。
血管紧张素AT2受体在肾脏健康和疾病中的作用的最新发现强烈表明,用选择性激动剂对该受体进行药物靶向治疗是一种有前景的治疗策略,可用于诱导利尿/尿钠排泄(也可与现有利尿剂相加)以及治疗糖尿病肾病或其他发病机制的肾脏疾病。