title: Evaluation of subacute change in RAAS activity (as indicated by urinary aldosterone:creatinine, after pharmacologic provocation) and the response to ACE inhibition.
abstract: OBJECTIVE
  The objective of this study was to evaluate subacute changes in renin-angiotensin-aldosterone system (RAAS) activity during angiotensin-converting enzyme inhibitor (ACEI) therapy in dogs with experimental RAAS activation.
  
  
  METHODS
  Analysis of data (urine aldosterone:creatinine ratio (UAldo:C) and serum angiotensin-converting enzyme activity), in 31 healthy dogs with furosemide or amlodipine-activated RAAS that received an ACEI. When furosemide or amlodipine activation of RAAS preceded ACEI administration, incomplete RAAS blockade (IRB) was defined as a UAldo:C greater than (a) the dog's 'activated' baseline value or (b) a population-derived cut-off value (mean + 2 SD (>1.0 μg/g) of pretreatment UAldo:C from our population of research dogs). In studies where RAAS activation occurred concurrently with ACEIs, IRB was defined as (a) a UAldo:C greater than either twofold the dog's prestimulation baseline value or (b) 1.0 µg/g. Dogs were followed for 7-17 days.
  
  
  RESULTS
  Serum angiotensin-converting enzyme activity was measured in 19 dogs and was significantly reduced (P<0.0001) after ACEI administration. The overall incidence of IRB, when RAAS activation preceded ACEI administration, was 33% and 8% for definitions (a) and (b), respectively. The overall incidence of IRB, when ACEIs were concurrent with RAAS activation, was 65% and 61% for definitions (a) and (b), respectively.
  
  
  CONCLUSIONS
  Increases in UAldo:C, despite ACEI administration, is evidence of IRB in this subacute model of experimental RAAS activation and suppression.
authors.affiliation: Department of Clinical Sciences, Colorado State University, USA marisa.ames@colostate.edu.
authors.forename: Marisa K
authors.initials: MK
authors.lastname: Ames
authors.affiliation: Department of Clinical Sciences, North Carolina State University, USA.
authors.forename: Clarke E
authors.initials: CE
authors.lastname: Atkins
authors.affiliation: Veterinary Emergency and Referral Group, New York, USA.
authors.forename: Andrea C
authors.initials: AC
authors.lastname: Lantis
authors.affiliation: Department of Statistics, Colorado State University, USA.
authors.forename: James
authors.initials: J
authors.lastname: zum Brunnen
mesh_terms: D000450:Aldosterone / Q000652:urine*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D003404:Creatinine / Q000652:urine*; D004285:Dogs; D005260:Female; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000450:Aldosterone; D003404:Creatinine; D007703:Peptidyl-Dipeptidase A
keywords: Aldosterone breakthrough; RAAS activation; angiotensin-converting enzyme inhibitors; heart failure; mineralocorticoid receptor blockers