The renin-angiotensin system (RAS) is a major physiological regulator of body fluid volume, electrolyte balance, and arterial blood pressure. Systemic suppression of the RAS through angiotensin converting-enzyme (ACE) inhibition and/or angiotensin receptor blockade (ARB) is an established and effective therapeutic approach for a range of cardiovascular disorders. One of the functions of renin is to catalyze the cleavage of angiotensinogen to angiotensin I (Ang I), which is the first and rate-limiting step of the RAS. Ang I is then converted by ACE to angiotensin II (Ang II), a potent endogenous vasoconstrictor. Interruption of the formation of Ang II by renin inhibitors offers a therapeutic profile that is distinct from that of the more well-known RAS antagonists, since both ACE inhibition (via ACE-independent pathways) and ARB, result in an increase in Ang II formation. This review will focus on the development and relevant clinical studies involving the renin inhibitors. The therapeutic implications of renin inhibitors, either employed alone, or in combination with ACE inhibitors or ARBs, will also be discussed.
Keywords: plasma renin activity, angiotensin converting enzyme inhibitor, Aliskiren, mild to moderate hypertension, enalapril
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