title: Maximally recommended doses of angiotensin-converting enzyme (ACE) inhibitors do not completely prevent ACE-mediated formation of angiotensin II in chronic heart failure.
abstract: BACKGROUND
  The added benefits of angiotensin II type I receptor (AT(1)) blockers (ARBs) to ACE inhibition suggests that recommended doses of ACE inhibitors provide only partial inhibition of ACE in chronic heart failure (CHF). Accordingly, the level of ACE inhibition was assessed by the pressor response to angiotensin (Ang) I in patients who had been treated with recommended doses of ACE inhibitors.
  
  
  RESULTS
  Forty-two patients with CHF receiving 40 mg/d of a long-acting ACE inhibitor or 150 mg of captopril were studied. Radial artery systolic pressure (RASP, mm Hg) was monitored noninvasively. The pressor response to ascending doses of Ang I was evaluated in all patients before and after administration of the ARB valsartan. The pressor response to Ang I before and after valsartan was also reevaluated in 11 patients after the dose of ACE inhibitor was doubled for 1 week. RASP increased linearly with significantly ascending doses of Ang I despite treatment with ACE inhibitors. The pressor response to Ang I was blunted significantly by valsartan. Ang I-induced increase in RASP did not correlate with duration of ACE inhibitor therapy. After the dose of ACE inhibitors was doubled, the pressor response to Ang I was no longer different from that noted after valsartan.
  
  
  CONCLUSIONS
  Recommended doses of ACE inhibitors do not fully inhibit ACE in CHF. The level of ACE inhibition achieved is not related to duration of ACE inhibitor therapy. Greater ACE inhibition is also achieved at twice the recommended doses of ACE inhibitors.
authors.affiliation: Department of Medicine, Division of Cardiology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: U P
authors.initials: UP
authors.lastname: Jorde
authors.forename: P V
authors.initials: PV
authors.lastname: Ennezat
authors.forename: J
authors.initials: J
authors.lastname: Lisker
authors.forename: V
authors.initials: V
authors.lastname: Suryadevara
authors.forename: J
authors.initials: J
authors.lastname: Infeld
authors.forename: S
authors.initials: S
authors.lastname: Cukon
authors.forename: A
authors.initials: A
authors.lastname: Hammer
authors.forename: E H
authors.initials: EH
authors.lastname: Sonnenblick
authors.forename: T H
authors.initials: TH
authors.lastname: Le Jemtel
mesh_terms: D000803:Angiotensin I / Q000008:administration & dosage / Q000494:pharmacology*; D000804:Angiotensin II / Q000096:biosynthesis*; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D017328:Fosinopril / Q000008:administration & dosage / Q000627:therapeutic use; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D017706:Lisinopril / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000187:drug effects; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D017211:Treatment Failure; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000068756:Valsartan
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; D004656:Enalapril; D000068756:Valsartan; D000803:Angiotensin I; D017706:Lisinopril; D007703:Peptidyl-Dipeptidase A; D014633:Valine; D017328:Fosinopril