Novel aspects of the renin-angiotensin-aldosterone-system.
The renin-angiotensin-aldosterone system (RAAS) play a pivotal role in the progression of renal disease. The RAAS has become much more complex in recent years with the identification of novel peptides that exhibit biological activity. There are novel pathways of angiotensin II (ANG II) generation independent of angiotensin converting enzyme (ACE). ANG II bind to at least two different receptors and prorenin/renin also exerts pathophysiological effects through binding to specific receptor. ANG II itself has emerged as a multifunctional cytokine exhibiting many non-hemodynamic properties such as acting as a growth factor and profibrogenic and proinflammatory cytokine. These profibrogenic and proinflammatory effects are mediated by other factors such as transforming growth-factor beta (TGF-beta) and chemoattractants that are induced in the kidney by ANG II. Increased aldosterone levels contribute to renal injury, independent of blood pressure or ANG II. Numerous experimental and clinical studies have shown that ACE-inhibitors as well as AT1-receptor antagonists can prevent glomerulosclerosis and tubulointerstitial fibrosis. This review will highlight some of these novel insights into the RAAS in regards to renal injury.
Wolf
Gunter
G
Department of Internal Medicine III, Friedrich-Schiller-University, Jena, Germany. gunter.wolf@med.uni-jena.de
D000450:Aldosterone / Q000502:physiology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D006801:Humans; D007674:Kidney Diseases / Q000188:drug therapy / Q000503:physiopathology*; D007676:Kidney Failure, Chronic / Q000188:drug therapy / Q000503:physiopathology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011945:Receptors, Angiotensin / Q000502:physiology; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D011945:Receptors, Angiotensin; D000450:Aldosterone; D007703:Peptidyl-Dipeptidase A