Document Detail

Bradykinin pathway is involved in acute hemodynamic effects of enalaprilat in dogs with heart failure.
MedLine Citation:
PMID:  8764248     Owner:  NLM     Status:  MEDLINE    
To determine the role of the renin-angiotensin system and the bradykinin pathway in the mechanism of action of angiotensin-converting enzyme inhibitors in heart failure, the acute effects of enalaprilat (1 mg/kg) were compared with those of a renin inhibitor (ciprokiren, 1 mg/kg i.v.) in 10 chronically instrumented conscious dogs with heart failure induced by right ventricular pacing (3 wk, 240 beats/min). The effects of enalaprilat and ciprokiren on bradykinin infusion (3, 10, and 30 micrograms/min) and the effects of enalaprilat in the presence of the bradykinin B2 receptor antagonist Hoe-140 (10 micrograms/kg i.v.) were also examined. Both inhibitors significantly decreased mean aortic pressure and increased cardiac output. However, enalaprilat induced significantly greater hemodynamic effects than ciprokiren (mean aortic pressure, -13 +/- 3 vs. -6 +/- 1 mmHg; cardiac output, 0.4 +/- 0.1 vs. 0.15 +/- 0.1 l/min). Bradykinin infusion led to dose-dependent decreases in mean aortic pressure and increases in cardiac output that were not modified by pretreatment with ciprokiren but were potentiated 10-fold by enalaprilat. Hoe-140 significantly reduced the hemodynamic effects of enalaprilat. Thus endogenous bradykinin is involved in the acute hemodynamic effects of enalaprilat in experimental heart failure.
F Barbe; J B Su; T T Guyene; B Crozatier; J Ménard; L Hittinger
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The American journal of physiology     Volume:  270     ISSN:  0002-9513     ISO Abbreviation:  Am. J. Physiol.     Publication Date:  1996 Jun 
Date Detail:
Created Date:  1996-09-19     Completed Date:  1996-09-19     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0370511     Medline TA:  Am J Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  H1985-92     Citation Subset:  IM    
Institut National de la santé et de la Recherche Médicale, Faculté de Médecine, Créteil, France.
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MeSH Terms
Angiotensin-Converting Enzyme Inhibitors / pharmacology*
Bradykinin / analogs & derivatives,  metabolism*,  pharmacology,  physiology
Cardiac Output, Low / blood,  physiopathology*
Enalaprilat / pharmacology*
Hemodynamics / drug effects*,  physiology
Hormones / blood
Imidazoles / pharmacology
Receptors, Bradykinin / antagonists & inhibitors
Renin / antagonists & inhibitors
Time Factors
Reg. No./Substance:
0/Angiotensin-Converting Enzyme Inhibitors; 0/Hormones; 0/Imidazoles; 0/Receptors, Bradykinin; 130308-48-4/icatibant; 143631-62-3/ciprokiren; 58-82-2/Bradykinin; 84680-54-6/Enalaprilat; EC

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