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Abstract

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 (AT₁) and angiotensin II type 2 (AT₂) receptors. The majority of the effects of angiotensin II, such as vasoconstriction, inflammation, and matrix deposition, are mediated via the AT₁ receptor. It is thought that the AT₂ receptor counteracts these effects and plays a role in nephroprotection. However, recent data support the notion that the AT₂ receptor transduces pro-inflammatory effects and promotes fibrosis and hypertrophy. Therefore, the question of whether stimulation of the AT₂ 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 AT₂ receptor-knockout mice demonstrate that the loss of AT₂ receptor signalling is associated with increased renal injury and mortality in chronic kidney disease. This raises the expectation that pharmacological stimulation of the AT₂ receptor may positively influence renal pathologies. However, further research is needed to explore the question whether AT₂ receptor stimulation may represent a new therapeutic strategy for the treatment of chronic kidney disease.

Keywords

angiotensin AT2 receptor fibrosis inflammation kidney

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The angiotensin II type 2 receptor in renal disease

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