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(Hypertension. 2008;52:467.)
© 2008 American Heart Association, Inc.

Editorial Commentaries

Aliskiren Improves Nitric Oxide Bioavailability and Limits Atherosclerosis

Subodh Verma; Milan K. Gupta

From the Division of Cardiac Surgery (S.V., M.K.G.), St Michael’s Hospital, University of Toronto, Toronto, Ontario; Canadian Cardiovascular Research Network (S.V., M.K.G.), Toronto, Ontario; and the Division of Cardiology (M.K.G.), McMaster University, Hamilton, Ontario, Canada.

Correspondence to Subodh Verma, Cardiac Surgeon, Associate Professor, Canada Research Chair in Atherosclerosis, St Michael’s Hospital, University of Toronto, Toronto, Ontario, Canada M5B 1W8. E-mail subodh.verma@sympatico.ca

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

Inhibition of the renin-angiotensin system (RAS), with angiotensin-converting enzyme inhibitor- (ACEI) and angiotensin receptor blocker (ARB)-based treatment approaches, has emerged as the cornerstone of contemporary cardiovascular risk reduction. These therapies offer robust reductions in cardiovascular mortality in patients postmyocardial infarction, those with systolic heart failure, and in high-risk patients with atherosclerosis. Furthermore, interruption of the RAS system has emerged as a critical modulator of normal and aberrant renal physiology, and interruption of RAS signaling is linked to improved renal structure and function.

The RAS supports a series of complex enzymatic reactions that culminate in the generation of angiotensin (Ang) II, the main effector molecule. Despite the success with conventional strategies to limit Ang II production and/or action, these agents promote a reflex rise in plasma renin activity (PRA), which may serve to sustain ongoing RAS activation. Although the predictive value of PRA remains debatable, it does predict myocardial infarction in stroke survivors enrolled in the Perindopril Protection Against Recurrent Stroke Study (PROGRESS).¹ As such, if PRA is predictive of risk in a population of patients with vascular disease, this may represent residual risk and serve as a novel target of therapy by agents that inhibit renin and neutralize the compensatory rise in PRA. Experimental and early clinical studies with aliskiren, the first commercially available direct renin inhibitor, suggest that it limits this negative feedback rise in PRA and Ang II that occurs during treatment with ACEI- or ARB-based therapies and, therefore, may allow for more complete blockade of the RAS.² . . . [Full Text of this Article]

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Renin Inhibitor Aliskiren Improves Impaired Nitric Oxide Bioavailability and Protects Against Atherosclerotic Changes

Toshio Imanishi, Hiroto Tsujioka, Hideyuki Ikejima, Akio Kuroi, Shigeho Takarada, Hironori Kitabata, Takashi Tanimoto, Yasuteru Muragaki, Seiichi Mochizuki, Masami Goto, Kiyoshi Yoshida, and Takashi Akasaka
Hypertension 2008 52: 563-572. [Abstract] [Full Text] [PDF]