[The renin-angiotensin-aldosterone system -- more complex as previously thought].
BACKGROUND
Angiotensin II (ANG II) is an important factor for the progression of renal diseases. ANG II has many pleiotropic effects on the kidney such as pro-inflammatory and profibrotic actions besides the well-known blood pressure-increasing effect.
Organs have local ANG II-generating systems that work independently from their classic systemic counterpart. Renal proximal tubular cells could generate and secrete ANG II into the urine in concentrations that are 10,000 times higher than those found in serum. These local systems are only incompletely blocked by currently used doses of ACE inhibitors or AT(1) antagonists. There are other enzyme systems besides ACE that contribute to the formation of ANG II. Alternative pathways generate peptides such as angiotensin 1-7 that have antagonistic effect compared with ANG II. Degradation products of ANG II such as angiotensin IV bind at separate receptors and could mediate fibrosis. The discovery of AT(1) receptor dimers and agonistic antibodies against AT(1) receptors contributes to the complexity of the system.


CONCLUSIONS
The complexity of the renin-angiotensin-aldosterone system (RAAS) implies that dual blockade with ACE inhibitors and AT(1) receptor antagonists makes sense for pathophysiological reasons. First clinical studies have shown that such as dual therapy reduces progression of chronic renal disease more efficiently that the respective monotherapies in certain risk populations. This shows that novel pathophysiological data could lead to innovative clinical treatment strategies.
Wolf
Gunter
G
Klinik für Innere Medizin III, Klinikum der Friedrich-Schiller-Universität Jena, Jena. Gunter.Wolf@med.uni-jena.de
D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism / Q000502:physiology* / Q000652:urine; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D002908:Chronic Disease; D053818:Chymases; D002986:Clinical Trials as Topic; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000503:physiopathology; D018450:Disease Progression; D004359:Drug Therapy, Combination; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D007674:Kidney Diseases / Q000188:drug therapy* / Q000503:physiopathology*; D007687:Kidney Tubules, Proximal / Q000502:physiology; D019808:Losartan / Q000008:administration & dosage / Q000627:therapeutic use; D011446:Prospective Studies; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000502:physiology; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology*; D012307:Risk Factors; D012697:Serine Endopeptidases / Q000378:metabolism
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D007211:Indoles; D011945:Receptors, Angiotensin; D000804:Angiotensin II; C052035:trandolapril; C012877:angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-; D000803:Angiotensin I; D012697:Serine Endopeptidases; D053818:Chymases; D019808:Losartan