Document Detail


Differential actions of vasopeptidase inhibition versus angiotensin-converting enzyme inhibition on diuretic therapy in experimental congestive heart failure.
MedLine Citation:
PMID:  11827932     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Omapatrilat (OMA), a vasopeptidase inhibitor, simultaneously inhibits angiotensin-converting enzyme (ACE) and neutral endopeptidase, which degrades vasodilatory factors (eg, ADM) and natriuretic peptides. Based on the beneficial cardiorenal and humoral properties of the natriuretic peptides, we hypothesized that an acute vasopeptidase inhibitor with or without diuretic would result in more favorable cardiorenal and hormonal actions than ACE inhibition plus diuretic (ACEI+D) in congestive heart failure. METHODS AND RESULTS: We compared the actions of OMA alone and with diuretic (OMA+D) to ACEI+D in a model of pacing-induced congestive heart failure. OMA+D decreased pulmonary arterial and pulmonary capillary wedge pressures to a greater level than OMA alone or ACEI+D. Glomerular filtration rate was lower with ACEI+D than with either OMA group. Plasma renin activity and aldosterone immediately increased with ACEI+D, whereas OMA+D resulted in higher plasma renin activity and a delayed increase in aldosterone. OMA alone did not increase plasma renin activity and aldosterone, but resulted in a sustained increase in plasma adrenomedullin, with higher urinary atrial natriuretic peptide, adrenomedullin, and cGMP excretions than with ACEI+D. CONCLUSIONS: Acute administration of OMA with or without diuretic results in more favorable cardiorenal and humoral responses in experimental congestive heart failure than does ACEI+D. There is no acute activation of renin and aldosterone with OMA alone such as occurs with ACEI+D and OMA+D. Thus, OMA with or without a diuretic possesses beneficial cardiorenal and humoral actions comparable to those observed with ACEI+D that can be explained by potentiation of natriuretic peptides.
Authors:
Alessandro Cataliotti; Guido Boerrigter; Horng H Chen; Michihisa Jougasaki; Lisa C Costello; Toshihiro Tsuruda; Shang-Chiun Lee; Lorenzo S Malatino; John C Burnett
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Circulation     Volume:  105     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2002 Feb 
Date Detail:
Created Date:  2002-02-05     Completed Date:  2002-02-12     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  639-44     Citation Subset:  AIM; IM    
Affiliation:
Cardiorenal Research Laboratory, Department of Physiology and Internal Medicine, Mayo Clinic and Foundation, Rochester, Minnesota, USA. cataliotti.alessandro@mayo.edu
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MeSH Terms
Descriptor/Qualifier:
Adrenomedullin
Aldosterone / blood
Angiotensin-Converting Enzyme Inhibitors / pharmacology*
Animals
Atrial Natriuretic Factor / urine
Cardiac Pacing, Artificial
Cyclic GMP / urine
Disease Models, Animal
Diuretics / pharmacology*
Dogs
Drug Therapy, Combination
Glomerular Filtration Rate / drug effects
Heart Failure / drug therapy*,  physiopathology
Heart Function Tests / drug effects
Hemodynamics / drug effects
Kidney Function Tests
Male
Neprilysin / antagonists & inhibitors
Peptides / blood,  urine
Peptidyl-Dipeptidase A / metabolism
Protease Inhibitors / pharmacology*
Pulmonary Wedge Pressure / drug effects
Pyridines / pharmacology*
Renin / blood
Thiazepines / pharmacology*
Treatment Outcome
Grant Support
ID/Acronym/Agency:
HL-07111/HL/NHLBI NIH HHS; HL-36634/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Angiotensin-Converting Enzyme Inhibitors; 0/Diuretics; 0/Peptides; 0/Protease Inhibitors; 0/Pyridines; 0/Thiazepines; 0/omapatrilat; 148498-78-6/Adrenomedullin; 52-39-1/Aldosterone; 7665-99-8/Cyclic GMP; 85637-73-6/Atrial Natriuretic Factor; EC 3.4.15.1/Peptidyl-Dipeptidase A; EC 3.4.23.15/Renin; EC 3.4.24.11/Neprilysin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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