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(Hypertension. 2005;46:471.)
© 2005 American Heart Association, Inc.

Editorial Commentaries

Renin Inhibition

New Potential for an Old Therapeutic Target

Darren J. Kelly; Jennifer L. Wilkinson-Berka; Richard E. Gilbert

From the Department of Medicine (D.J.K., R.E.G.), St Vincent’s Hospital, and the Department of Physiology (J.L.W.-B.), The University of Melbourne, Parkville, Victoria, Australia.

Correspondence to Darren J. Kelly, Department of Medicine, St Vincent’s Hospital, The University of Melbourne, Cnr Princes and Regent Sts, Fitzroy, 3065, Victoria, Australia. E-mail dkelly@medstv.unimelb.edu.au

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Experimental and clinical studies have highlighted the importance of the local renin-angiotensin system (RAS) as a pathogenetic factor in various tissues, including the kidney, heart, and eye.¹ These studies have indicated that blockade of the RAS is an important therapeutic strategy in reducing cardiovascular and renal disease. However, the therapeutic response achieved with current blockers of the RAS—angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs)—although efficacious, is limited. This may be partly because of the reactive rise in renin that these agents induce with the resultant increase in angiotensin peptides. Other, more effective strategies to block the RAS have, therefore, been sought.

Angiotensin II, the major effector molecule of this system, is synthesized in a multistep process in which angiotensinogen is cleaved by the aspartic peptidase, renin, produced mainly in the juxtaglomerular cells of the kidney, to give to rise to angiotensin I. This biologically inactive decapeptide is then converted to the active octapeptide angiotensin II by ACE or by a range of other proteases.

Renin was first isolated from extracts of renal cortex, where its pressor effect was noted following intravenous injection.² More than a century later the physiological and pathological significance of renin is still being unraveled. For instance, a renin receptor in the kidney and vasculature has recently been identified.³ Binding of renin to this receptor not only increases its catalytic efficiency in angiotensin I formation, but also converts the otherwise inert prorenin into an active moiety. Moreover, the interaction between renin or prorenin with its . . . [Full Text of this Article]

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