title: Inhibition of renin: an updated review of the development of renin inhibitors.
abstract: As an important cascade involved in the regulation of blood pressure and volume homeostasis, the renin-angiotensin system (RAS) has been targeted for blood pressure control. In the last decades, the most successful strategy to control the RAS has been the inhibition of the angiotensin-converting enzyme (ACE) and the angiotensin type 1 (AT(1)) receptor. Small-molecule inhibitors targeting these steps have been widely used clinically. However, complete inhibition of the RAS is not achievable by blocking the ACE or the AT(1) because of the compensatory rise in plasma renin activity, which limits the efficacy of many RAS drugs. Direct inhibition of renin, the first and rate-limiting step in the RAS cascade, is the preferred strategy for controlling the RAS, and much progress has been made in the research and development of renin inhibitors. This review covers the evolution of renin inhibitors and discusses the advantages of renin inhibition at the enzymatic and biosynthetic levels for blood pressure control.
authors.affiliation: The University of Chicago, Department of Medicine, MC 4076, 5841 S Maryland Avenue, Chicago, IL 60637, USA. cyan@medicine.bsd.uchicago.edu
authors.forename: Yan Chun
authors.initials: YC
authors.lastname: Li
mesh_terms: D000577:Amides / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005650:Fumarates / Q000494:pharmacology; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D015394:Molecular Structure; D010455:Peptides / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000378:metabolism; D012083:Renin / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects*; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism; D014807:Vitamin D / Q000031:analogs & derivatives / Q000494:pharmacology; D000092502:Renin Inhibitors; D000093342:Prorenin Receptor
chemical_list: D000577:Amides; D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000906:Antibodies; D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D005650:Fumarates; D010455:Peptides; D011956:Receptors, Cell Surface; D012083:Renin; D025262:Vacuolar Proton-Translocating ATPases; D014807:Vitamin D; D000092502:Renin Inhibitors; C458319:ATP6AP2 protein, human; D000093342:Prorenin Receptor; C446481:aliskiren