Document Detail


Angiotensinergic versus nonangiotensinergic hemodynamic effects of converting enzyme inhibition in patients with chronic heart failure. Assessment by acute renin and converting enzyme inhibition.
MedLine Citation:
PMID:  7994817     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: The contribution of nonangiotensinergic effects of converting enzyme inhibitors to their hemodynamic effects in patients with chronic heart failure is not clear. A comparison of the effects of renin and converting enzyme inhibition should help to clarify this issue. METHODS AND RESULTS: Thirty-six patients with chronic heart failure (New York Heart Association class II or III) were randomly assigned to receive double-blind either intravenous placebo, the renin inhibitor remikiren, or the converting enzyme inhibitor enalaprilat followed by coinfusion of a second placebo infusion, the addition of remikiren to enalaprilat, or the addition of enalaprilat to remikiren, respectively. Systemic hemodynamics (Swan-Ganz and radial artery catheters) were measured before (rest and submaximal recumbent bicycle ergometry), during (rest), and at the end (rest and exercise) of each 45-minute single- or combination-infusion period. Placebo did not change hemodynamics or renin activity. Effective inhibition of the renin-angiotensin system by remikiren and enalaprilat was indicated by increases of plasma immunoreactive renin together with rapid and complete inhibition of renin activity after remikiren and an increase after enalaprilat (all P < or = .05). Remikiren and enalaprilat rapidly and to a similar extent reduced resting blood pressure through a reduction of systemic vascular resistance, and these changes were significantly correlated to baseline plasma renin activity. Both compounds also decreased pulmonary artery, pulmonary capillary wedge, and right atrial pressures to a similar extent (P < .05). During exercise, pulmonary capillary wedge and right atrial pressures were equally reduced and stroke volume index was increased with remikiren and enalaprilat (P < .05) for both). The combination of converting enzyme with renin inhibition or vice versa did not cause additional hemodynamic changes. CONCLUSIONS: Specific renin inhibition in patients with chronic heart failure produces short-term hemodynamic effects that are almost indistinguishable from those of converting enzyme inhibition. This finding and the lack of additional effects of converting enzyme inhibition added to renin inhibition suggest that nonangiotensinergic effects of converting enzyme inhibitors do not play a significant role in their short-term hemodynamic effects in patients with chronic heart failure.
Authors:
W Kiowski; J Beermann; P Rickenbacher; R Haemmerli; M Thomas; F Burkart; T Meinertz
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Publication Detail:
Type:  Clinical Trial; Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Circulation     Volume:  90     ISSN:  0009-7322     ISO Abbreviation:  Circulation     Publication Date:  1994 Dec 
Date Detail:
Created Date:  1995-01-17     Completed Date:  1995-01-17     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2748-56     Citation Subset:  AIM; IM    
Affiliation:
Division of Cardiology, University Hospital, Basel, Switzerland.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
Cardiac Output, Low / drug therapy*
Chronic Disease
Double-Blind Method
Drug Therapy, Combination
Enalaprilat / therapeutic use*
Female
Hemodynamics / drug effects*
Humans
Imidazoles / therapeutic use*
Male
Middle Aged
Renin / antagonists & inhibitors*,  blood
Chemical
Reg. No./Substance:
0/Angiotensin-Converting Enzyme Inhibitors; 0/Imidazoles; 135669-48-6/remikiren; 84680-54-6/Enalaprilat; EC 3.4.23.15/Renin

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