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(Hypertension. 2008;52:563.)
© 2008 American Heart Association, Inc.

Original Articles

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; Takashi Akasaka

From the Departments of Cardiovascular Medicine (T.I., H.T., H.I., A.K., S.T., H.K., T.T., T.A.) and Pathology (Y.M.), Wakayama Medical University, Wakayama, Japan; and the Department of Medical Engineering (S.M., M.G.) and Division of Cardiology (K.Y.), Kawasaki Medical School, Okayama, Japan.

Correspondence to Toshio Imanishi, Department of Cardiovascular Medicine, Wakayama Medical University, 811-1, Kimiidera, Wakayama City, Wakayama 641-8510, Japan. E-mail t-imani{at}wakayama-med.ac.jp

We investigated whether aliskiren, a direct renin inhibitor, improves NO bioavailability and protects against spontaneous atherosclerotic changes. We also examined the effects of cotreatment with aliskiren and valsartan, an angiotensin II receptor blocker, on the above-mentioned outcomes. Watanabe heritable hyperlipidemic rabbits were treated with vehicle (control), aliskiren, valsartan, or aliskiren plus valsartan for 8 weeks. Then, acetylcholine-induced NO production was measured as a surrogate index of endothelium protective function, and both superoxide and vascular peroxynitrite were measured. Tetrahydrobiopterin in aortic segments was assessed by high-performance liquid chromatography with fluorescence detection. Plaque area was quantified by histology. Increase in plasma NO concentration in response to intra-aortic acetylcholine infusion was significantly greater in all of the test groups than in controls. Aliskiren+valsartan cotreatment increased acetylcholine-induced NO by 6.2 nmol/L, which was significantly higher than that with either aliskiren or valsartan alone. Vascular superoxide and peroxynitrite levels were both significantly higher in controls and significantly lower in the aliskiren+valsartan group than in the aliskiren or valsartan group. The highest tetrahydrobiopterin levels were observed after aliskiren+valsartan cotreatment. Histology of the thoracic aorta revealed that the plaque area was significantly decreased with combination therapy compared with monotherapy. Treatment with a direct renin inhibitor has protective effects on endothelial function and atherosclerotic changes. Furthermore, cotreatment with a direct renin inhibitor and an angiotensin II receptor blocker has additive protective effects on both.

Key Words: NO • endothelial function • renin inhibitor • oxidative stress

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Aliskiren Improves Nitric Oxide Bioavailability and Limits Atherosclerosis

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