Inhibition of the renin angiotensin aldosterone system: focus on aliskiren

Maddury Srinivasa Rao
Journal of the Association of Physicians of India 2010, 58: 102-8
The renin-angiotensin system (RAS) or the renin-angiotensin-aldosterone system (RAAS) is a major endocrine/paracrine system that regulates blood pressure (BP) via angiotensin release and fluid and electrolyte homoeostasis via aldosterone release. RAAS should be constantly suppressed and any degree of activity may lead to hypertension (HTN) and associated target organ damage. Activation of the RAAS in the pathogenesis of HTN, CVD and renal disease is well documented. Also benefits of inhibition of RAAS, as an effective way to intervene in pathogenesis HTN, CVD and CRF, has been well recognized. RAAS may be blocked by drugs at various points and is important target site for five distinctive classes of hypertensive drugs; beta blockers, renin inhibitors, angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) and aldosterone inhibitors. Inhibition of renin activity and the blocked of RAAS cascade at its primary steps, has long been proposed as the optimal means of RAAS Inhibition. Renin inhibitor provides more effective means of RAAS Inhibition. Aliskiren is the first in a new class of orally active, non-peptide, low molecular weight direct renin inhibitor (DRI) available for clinical use and potential new approach to the blockade of the RAAS. An average plasma half-life of 23.7 hours (range 20-45 hours), makes drug suitable for once daily administration. BP-lowering affect of aliskiren is associated with a decreased, not increased, generation of Ang I, as it blocks generation of Ang I from angiotensinogen, by inhibiting the active enzymatic site of renin. Aliskiren has generally been well tolerated with adverse events and discontinuation rates similar to placebo in most clinical trials. Aliskiren has the potential to be useful in this wide spectrum of conditions and may provide organ protection independent of BP reductions.

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