The angiotensin type 2 receptor and the kidney

Curr Opin Nephrol Hypertens. 2017 Jan;26(1):36-42. doi: 10.1097/MNH.0000000000000289.

Abstract

Purpose of review: 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.

Recent findings: 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.

Summary: 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.

Publication types

  • Review

MeSH terms

  • Animals
  • Diabetic Nephropathies / drug therapy
  • Diabetic Nephropathies / metabolism*
  • Diuresis
  • Humans
  • Kidney Tubules, Proximal / metabolism*
  • Natriuresis
  • Obesity / metabolism*
  • Receptor, Angiotensin, Type 2 / agonists
  • Receptor, Angiotensin, Type 2 / metabolism*
  • Sex Factors
  • Sodium-Hydrogen Exchanger 3 / antagonists & inhibitors
  • Sodium-Potassium-Exchanging ATPase / antagonists & inhibitors

Substances

  • Receptor, Angiotensin, Type 2
  • SLC9A3 protein, human
  • Sodium-Hydrogen Exchanger 3
  • Sodium-Potassium-Exchanging ATPase