New Approaches to Blockade of the Renin-Angiotensin-Aldosterone System: Characteristics and Usefulness of the Direct Renin Inhibitor Aliskiren

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  • Ichihara Atsuhiro
    Departments of Anti-Aging Medicine & Endocrinology and Internal Medicine, Keio University School of Medicine, Japan
  • Sakoda Mariyo
    Departments of Anti-Aging Medicine & Endocrinology and Internal Medicine, Keio University School of Medicine, Japan
  • Kurauchi-Mito Asako
    Departments of Anti-Aging Medicine & Endocrinology and Internal Medicine, Keio University School of Medicine, Japan
  • Narita Tatsuya
    Departments of Anti-Aging Medicine & Endocrinology and Internal Medicine, Keio University School of Medicine, Japan
  • Kinouchi Kenichiro
    Departments of Anti-Aging Medicine & Endocrinology and Internal Medicine, Keio University School of Medicine, Japan
  • Bokuda Kanako
    Departments of Anti-Aging Medicine & Endocrinology and Internal Medicine, Keio University School of Medicine, Japan
  • Itoh Hiroshi
    Departments of Anti-Aging Medicine & Endocrinology and Internal Medicine, Keio University School of Medicine, Japan

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  • Characteristics and usefulness of the direct renin inhibitor aliskiren

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Abstract

Since renin inhibition interferes with the first and rate-limiting steps in the renin–angiotensin system, the renin step is a very attractive target for lowering blood pressure and minimizing target-organ damage. The newly developed direct renin inhibitor aliskiren has several attractive characteristics: it definitively reduces plasma renin activity among inhibitors of the renin–angiotensin system, is remarkably specific for human renin, exhibits a long half-life in plasma comparable to that of amlodipine, and has a high affinity for renal glomeruli and vasculature. Although these characteristics suggest the clinical usefulness and safety of aliskiren, several problems remain unsolved. Why does aliskiren have beneficial effects on the heart and kidneys of patients treated with angiotensin-converting enzyme (ACE) inhibitors and/or angiotensin II type 1–receptor blockers (ARBs)? Is the blood-pressure–lowering effect of aliskiren dependent on the plasma renin activity? Does aliskiren exert a possible adverse effect via (pro)renin receptor–dependent intracellular signals? Here, we review the characteristics and usefulness of aliskiren and discuss the current issues associated with this direct renin inhibitor.

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