title: Modulation of the renin-angiotensin-aldosterone system in sepsis: a new therapeutic approach?
abstract: BACKGROUND
  Severe sepsis is characterized by relative hypotension associated with a high cardiac output, peripheral vasodilation, and organ dysfunction. The renin-angiotensin-aldosterone system (RAAS) is primarily activated to increase blood pressure, but recently potential pro-inflammatory effects of angiotensin II have attracted interest because of the reported association between angiotensin II levels and organ failure and mortality in sepsis. RAAS antagonists could represent a new therapeutic option in this setting.
  
  
  METHODS
  The role of RAAS activation in severe sepsis and septic shock, and the potential benefits (and risks) of using RAAS antagonists.
  
  
  RESULTS
  Insight into RAAS function in severe sepsis and the potential for RAAS inhibitors to be used as an adjunctive therapy in patients with severe sepsis, with discussion of promising results from animal models of sepsis.
  
  
  CONCLUSIONS
  Use of RAAS antagonists is an emerging therapeutic option in severe sepsis because these agents may reduce endothelial damage, organ failure, and mortality. However, timing of administration of RAAS antagonists is important because reduced RAAS function may contribute to refractive hypotension later on in septic shock and benefits of RAAS antagonists seem to be restricted to the early phases of sepsis.
authors.affiliation: Federal University of Rio de Janeiro, Clementino Fraga Filho University Hospital, Department of Internal Medicine, Cidade Universitària - Ilha do Fundão - Rio de Janeiro, Brazil. d.salgado@globo.com
authors.forename: Diamantino Ribeiro
authors.initials: DR
authors.lastname: Salgado
authors.forename: José Rodolfo
authors.initials: JR
authors.lastname: Rocco
authors.forename: Eliézer
authors.initials: E
authors.lastname: Silva
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Vincent
mesh_terms: D000804:Angiotensin II / Q000502:physiology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism / Q000502:physiology; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology; D018805:Sepsis / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II