The Renin-Aldosterone System

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RAAS System
The renin-angiotensin-aldosterone system (RAAS) consists of a complex endocrine regulatory pathway and several less studied local autocrine/paracrine systems. RAAS is an important part of many pathologic conditions including hypertension, heart failure, and renal disease.
The classical endocrine RAAS is activated predominantly by decrease in renal blood flow. This system works primarily through the heart, blood vessels, and Kidneys to regulate blood pressure; and controls water and electrolyte balance.[figure 1] The RAAS contributes to chronic kidney disease(CKD) progression in part via blood pressure-mediated kidney damage. Angiotensin II, the primary effector agent of RAAS system, is a vasoconstrictor with a predominant effect …show more content…

2005) Local RAAS has been implicated as a key player in the pathogenesis of cardiovascular and renal diseases. Intrarenal RAAS is activated early in diabetic nephropathy, the leading cause of CKD.(Siragy and Carey 2010) Intracardiac RAAS may contribute to myocardial hypertrophy and remodeling.(Hayashida et al. 1993) Production of Aldosterone and Angiotensin Converting Enzyme (ACE) and selective downregulation of specific angiotensin II receptors has been observed in the failing heart(Mizuno et al. 2001)(Silvestre et al. 1999) (Asano et al. 1997)(Haywood et al. 1997)(Zisman et al. 1998). In addition to their direct effects, RAAS elements may also have indirect pathological effects through influencing factors like sympathetic activity(Grassi et al. 1997)(Dibner-Dunlap et al. 1996)(Latini 2002) level of kinins(Witherow et al. 2001), endothelial function(Hornig et al. 1998)(Clavell et al. 1996), and/or cytokine levels. (Gullestad et al. 1999)(Tsutamoto et al. …show more content…

The only approved in the last group is Aliskirin.

One of the major indications of RAAS inhibitors is blood pressure control. Despite all advances in medical sciences, 30.5% of men and 28.5% of women in the United States have hypertension.(Guo et al. 2012) The efficacy of ACEi and ARBs has shown to be similar to other first choice antihypertensive drugs, either as initial antihypertensive monotherapy or as a part of combination therapy of hypertension. In addition, there are a number of settings in which ACEi or ARBs are the antihypertensive drugs of choice because of possible benefits independent of blood pressure control.(Turnbull et al. 2008; Law, Morris, and Wald 2009) A comprehensive meta-analysis of 20 trials in RAAS inhibition proved that RAAS inhibition is associated with 5% decrease in all-cause mortality and 7% decrease in cardiovascular events in hypertensive patients(van Vark et al.

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