title: Effects of ACE inhibitors on cardiac angiotensin II and aldosterone in humans: "Relevance of lipophilicity and affinity for ACE".
abstract: BACKGROUND
  Angiotensin-converting enzyme (ACE) inhibitors differ in their lipophilic/hydrophilic index that determines their tissue bioavailability and affinity to ACE, which may result in major differences in the degree of blockade of cardiac ACE. We evaluated the hypothesis that in patients with chronic heart failure (CHF) and activated cardiac renin-angiotensin-aldosterone system (RAAS), lipophilic ACE inhibitors with high affinity for ACE (perindopril and quinapril) will cause marked blockade of cardiac angiotensin (Ang) II and aldosterone generation, but not a hydrophilic ACE inhibitor with low affinity for ACE (lisinopril).
  
  
  METHODS
  Patients were randomized to receive perindopril (8 mg/day), quinapril (40 mg/day), or lisinopril (20 mg/day) for 3-4 weeks before cardiac catheterization. The coronary sinus-aortic root gradients for Ang I and II, and aldosterone were determined.
  
  
  RESULTS
  A total of 19 patients completed the study. Compared to a healthy control group, all three ACE inhibitors decreased circulating Ang II and aldosterone to a similar extent. There were only minor differences between the three ACE inhibitors for the Ang II gradient between the coronary sinus and aortic root. The gradient for aldosterone tended to be positive in the quinapril group and absent/negative in the lisinopril and perindopril groups. Despite the lowest pulmonary capillary wedge pressure (PCWP), gradients between the coronary sinus and aortic root for Ang II and aldosterone were actually the highest in the quinapril group.
  
  
  CONCLUSIONS
  These findings do not support the concept that a hydrophilic ACE inhibitor is less effective in blocking the cardiac RAAS as compared to lipophilic ACE inhibitors.
authors.affiliation: University of Ottawa Heart Institute, Ontario, Canada. mruzicka@ottawahospital.on.ca
authors.forename: Marcel
authors.initials: M
authors.lastname: Ruzicka
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Coletta
authors.forename: Roselyn
authors.initials: R
authors.lastname: White
authors.forename: Ross
authors.initials: R
authors.lastname: Davies
authors.forename: Haissam
authors.initials: H
authors.lastname: Haddad
authors.forename: Frans H H
authors.initials: FH
authors.lastname: Leenen
mesh_terms: D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D001013:Aorta, Thoracic / Q000378:metabolism; D006328:Cardiac Catheterization; D054326:Coronary Sinus / Q000378:metabolism; D005260:Female; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D008055:Lipids / Q000737:chemistry; D017706:Lisinopril / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D020913:Perindopril / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D011446:Prospective Studies; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D000077583:Quinapril; D012084:Renin-Angiotensin System / Q000187:drug effects*; D044005:Tetrahydroisoquinolines / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D008055:Lipids; D044005:Tetrahydroisoquinolines; D000804:Angiotensin II; D000450:Aldosterone; D017706:Lisinopril; D000077583:Quinapril; D020913:Perindopril