The angiotensin II type 2 receptor in renal disease.
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.
Department of Medicine, Division of Nephrology, University Hospital Hamburg-Eppendorf, Hamburg, Germany. wenzel@uke.uni-hamburg.de
Ulrich Otto
UO
Wenzel
Christian
C
Krebs
Ralf
R
Benndorf
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology / Q000601:surgery; D007674:Kidney Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism*
D047228:Angiotensin II Type 1 Receptor Blockers; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2