Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Despite the existence of established, effective therapies for hypertension, new methods of blood pressure and cardiovascular risk reduction are still needed. Novel approaches are targeted towards treating resistant hypertension, improving blood-pressure control, and achieving further risk reduction beyond blood-pressure lowering. Modulation of the renin-angiotensin-aldosterone system (RAAS) provides the rationale for current antihypertensive therapies, including the relatively new agents eplerenone and aliskiren. Novel targets for antihypertensive therapy are also likely to be RAAS-related. The stimulation of angiotensin II type 2 receptors, or supplementation with renalase, could counteract the effects of angiotensin II type 1 receptor stimulation or catecholamine release. Combined angiotensin-converting-enzyme and neutral endopeptidase blockade decreases blood pressure, but is associated with a high incidence of angioedema. Aldosterone synthase inhibitors might improve tolerability in aldosterone antagonism. A (pro)renin-receptor blocker could prevent the deleterious angiotensin-independent actions of renin that are not inhibited by aliskiren. Finally, new minimally invasive surgical procedures have revived the concept of renal denervation, and could be a therapeutic option for patients with resistant hypertension. All of these strategies are exciting prospects, but which of them will prove valuable in clinical setting remains to be discovered.
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PMID:Novel therapeutic targets for hypertension. 2056 39

In liver cirrhosis, renin-angiotensin system (RAS) activation sustains renal sodium retention and hepatic fibrogenesis. New information has recently enlivened the traditional concept of RAS. For instance, renin and prorenin bind their ubiquitous receptors, resulting in the local production of angiotensin (Ang) II; increased serum calcium and calcimimetic agents, through stimulation of extracellular calcium-sensing receptors (CaSR), blunt renin production and lead to natriuretic effects in human and experimental cirrhosis. Alongside systemic production, there is Ang II tissue production within various organs through RAS enzymes different from angiotensin-converting enzyme (ACE), that is chymase, tissue plasminogen activator and several cathepsins. In experimental cirrhosis, inhibition of chymase leads to natriuretic and hepatic antifibrotic effects, without changes in systemic haemodynamics. In the kidney, local RAS coordinates proximal and distal tubular sodium reabsorption. However, renalase, whose plasma and tissue levels are severely altered in experimental cirrhosis, degrades systemic and renal tubule catecholamines, antagonizing the effects of renal RAS. Angiotensinogen-derived natriuretic and vasodilating peptides (Ang1-9, Ang1-7, Ang3-8) and their receptors have been described. Receptor agonists or antagonists are available to affect portal hypertension and sodium retention in cirrhosis. ACE2-dependent generation of Ang1-7 may inhibit experimental liver fibrosis. inhibition of Ang1-7 clearance by means of neprilysin blockade has portal hypotensive and natriuretic effects. Ang1-12, whose production renin does not regulate, is converted to several different angiotensin peptides via chymase. Finally, Ang II behaves as either an antinatriuretic or a natriuretic agent, based on the tissue content of AT1 R and AT2 R receptors, their ratio being prone to pharmacological modulation.
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PMID:Pathways of hepatic and renal damage through non-classical activation of the renin-angiotensin system in chronic liver disease. 3158 May 14