Renin inhibition--benefit beyond hypertension control.

The importance of the renin angiotensin system (RAS) in blood pressure and electrolyte regulation has been well established. High RAS activity results in over-activation of the angiotensin AT1-receptor by its substrate, angiotensin II (AII), leading to increases in BP and direct growth-promoting effects on tissues that result in end-organ damage. The antihypertensive therapies, such as ACE inhibitors and angiotensin AT1-receptor blockers (ARBs) have proved to be successful treatments for hypertension, heart failure, and other related cardiovascular and renal disorders. However, these compounds do not completely inhibit the RAS as a result of AII formation by indirect pathways and compensatory feedback mechanisms, resulting in renin release. Thus renin inhibition has been identified as the preferred pharmacologic approach to blockade of the renin-angiotensin system. The advantages of inhibiting renin in the RAS have been recognized for almost half a century; however major advances in the development of potential clinically effective renin inhibitors have been made only in the past few years with the approval of Aliskiren for clinical use.