TY - JOUR
AU1 - Zaman, Mohammad Amin
AU2 - Oparil, Suzanne
AU3 - Calhoun, David A.
AB - 


 Hypertension is the most common modifiable risk factor for cardiovascular disease (CVD), and the risk of CVD events, including myocardial infarction, stroke, heart failure and end-stage renal disease, can be greatly reduced by lowering blood pressure.


 The best-known regulator of blood pressure and determinant of target-organ damage from hypertension is the renin–angiotensin–aldosterone system (RAAS). Overexpression of renin and its metabolic products predisposes to hypertension and related target-organ damage.


 Renin cleaves angiotensinogen to produce the inactive peptide angiotensin I. Cleavage of angiotensin I by angiotensin-converting enzyme (ACE) gives the active peptide angiotensin II (although there are alternative routes). Most of the known functions of the RAAS are mediated through the activation of the angiotensin II type 1 receptor (AT1 receptor) by angiotensin II, which leads to vasoconstriction, aldosterone release and other functions that tend to elevate blood pressure and cause hypertrophy or hyperplasia of target cells.


 Approved drugs that act on the RAAS that are discussed here include ACE inhibitors, AT1-receptor blockers (ARBs) and aldosterone-receptor antagonists (ARAs). These agents have been shown to be highly effective in lowering blood pressure and, particularly in the case of the ARBs, are extremely well tolerated. A novel class of combined ACE and neutral-endopeptidase inhibitors that are in development, called vasopeptidase inhibitors, are also discussed.


 Clinical-trial evidence is beginning to clarify some of the key issues in the use of ACE inhibitors and ARBs, such as clinical benefits beyond blood-pressure lowering. These drugs are also helping to better define the role of the RAAS in the pathogenesis of hypertension, stroke, myocardial infarction, heart failure and end-stage renal disease.



TI - Drugs targeting the renin–angiotensin–aldosterone system
JF - Nature Reviews Drug Discovery
DO - 10.1038/nrd873
DA - 2002-08-01
UR - https://www.deepdyve.com/lp/springer-journals/drugs-targeting-the-renin-angiotensin-aldosterone-system-NA1j0AFpd0
SP - 621
EP - 636
VL - 1
IS - 8
DP - DeepDyve
ER -