Evaluation of subacute change in RAAS activity (as indicated by urinary aldosterone:creatinine, after pharmacologic provocation) and the response to ACE inhibition

J Renin Angiotensin Aldosterone Syst. 2016 Mar 23;17(1):1470320316633897. doi: 10.1177/1470320316633897. Print 2016 Jan-Mar.


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.

Conclusion: Increases in UAldo:C, despite ACEI administration, is evidence of IRB in this subacute model of experimental RAAS activation and suppression.

Keywords: Aldosterone breakthrough; RAAS activation; angiotensin-converting enzyme inhibitors; heart failure; mineralocorticoid receptor blockers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldosterone / urine*
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Animals
  • Creatinine / urine*
  • Dogs
  • Female
  • Male
  • Peptidyl-Dipeptidase A / blood
  • Renin-Angiotensin System / drug effects*


  • Angiotensin-Converting Enzyme Inhibitors
  • Aldosterone
  • Creatinine
  • Peptidyl-Dipeptidase A