title: Aminopeptidase A inhibitors as centrally acting antihypertensive agents.
abstract: Among the main bioactive peptides of the brain renin-angiotensin system, angiotensin (Ang) II and AngIII exhibit the same affinity for the type 1 and type 2 Ang receptors. Both peptides, injected intracerebroventricularly, cause similar increase in blood pressure (BP). Because AngII is converted in vivo to AngIII, the identity of the true effector is unknown. This review summarized recent insights into the predominant role of brain AngIII in the central control of BP underlining the fact that brain aminopeptidase A (APA), the enzyme forming central AngIII, could constitute a putative central therapeutic target for the treatment of hypertension. This led to the development of potent, systematically active APA inhibitors, such as RB150, as a prototype of a new class of centrally acting antihypertensive agents for the treatment of certain forms of hypertension.
authors.affiliation: U 691, Inserm, 11, Place Marcelin Berthelot, Paris Cedex 05, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Bodineau
authors.forename: Alain
authors.initials: A
authors.lastname: Frugière
authors.forename: Yannick
authors.initials: Y
authors.lastname: Marc
authors.forename: Cédric
authors.initials: C
authors.lastname: Claperon
authors.forename: Catherine
authors.initials: C
authors.lastname: Llorens-Cortes
mesh_terms: D000804:Angiotensin II / Q000378:metabolism / Q000502:physiology; D000805:Angiotensin III / Q000378:metabolism / Q000502:physiology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004220:Disulfides / Q000494:pharmacology / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D043384:Glutamyl Aminopeptidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008954:Models, Biological; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D013451:Sulfonic Acids / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000959:Antihypertensive Agents; D004220:Disulfides; D004791:Enzyme Inhibitors; D013451:Sulfonic Acids; D000804:Angiotensin II; D000805:Angiotensin III; C528573:firibastat; D043384:Glutamyl Aminopeptidase