Document Detail


Proinflammatory cytokines depress cardiac efficiency by a nitric oxide-dependent mechanism.
MedLine Citation:
PMID:  9724308     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Proinflammatory cytokines (interleukin-1beta, tumor necrosis factor-alpha, and interferon-gamma; Cytomix) depress myocardial contractile work partially by stimulating expression of inducible nitric oxide (NO) synthase (iNOS). Because NO and peroxynitrite inhibit myocardial O2 consumption (MVO2), we examined whether this mechanism contributes to reduced cardiac work. In control isolated working rat hearts, cardiac work was stable for 60 min, followed by a decline from 60 to 120 min, without change in MVO2. Cardiac efficiency (work/MVO2) was therefore reduced from 60 to 120 min. Cytomix shortened the onset (within 20-40 min) and enhanced the depression in cardiac work and efficiency and inhibited MVO2 after 80 min. Mercaptoethylguanidine (MEG), an iNOS inhibitor and peroxynitrite scavenger, or the glucocorticoid dexamethasone (Dex) abolished the effects of Cytomix. iNOS expression was increased 10-fold by Cytomix and abolished by Dex but not MEG. That cytokine-induced depression in cardiac work precedes the reduction in MVO2 suggests, at least in the early response, that NO and/or peroxynitrite may not impair heart function by inhibiting mitochondrial respiration but reduce the heart's ability to utilize ATP for contractile work.
Authors:
D Panas; F H Khadour; C Szabó; R Schulz
Related Documents :
10392878 - Study of myocardial contractility by pulsed wave doppler tissue imaging does not reveal...
12066558 - Myocardial hibernation.
7585818 - Effects of opc-18790, a new positive inotropic agent, on energetics in the ischaemic ca...
8863278 - Myocardial pharmacokinetics of thiopental in sheep after short-term administration: rel...
6225448 - Persistent left ventricular disease in clinically "cured" primary endocardial fibroelas...
2042788 - Magnesium inhibits the hypertensive but not the cardiotonic actions of low-dose epineph...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The American journal of physiology     Volume:  275     ISSN:  0002-9513     ISO Abbreviation:  Am. J. Physiol.     Publication Date:  1998 Sep 
Date Detail:
Created Date:  1998-10-01     Completed Date:  1998-10-01     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0370511     Medline TA:  Am J Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  H1016-23     Citation Subset:  IM    
Affiliation:
Departments of Pediatrics and Pharmacology, Cardiovascular Research Group, University of Alberta, Edmonton, Alberta, Canada T6G 2S2.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Coronary Circulation / drug effects
Dexamethasone / pharmacology
Enzyme Inhibitors / pharmacology
Free Radical Scavengers
Guanidines / pharmacology
Heart Conduction System / drug effects
Interferon-gamma / pharmacology*
Interleukin-1 / pharmacology*
Kinetics
Male
Myocardial Contraction / physiology*
Myocardium / metabolism
Nitrates / pharmacology
Nitric Oxide / pharmacology*
Nitric Oxide Synthase / antagonists & inhibitors,  metabolism
Nitric Oxide Synthase Type II
Oxygen Consumption / drug effects
Rats
Rats, Sprague-Dawley
Tumor Necrosis Factor-alpha / pharmacology*
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Free Radical Scavengers; 0/Guanidines; 0/Interleukin-1; 0/Nitrates; 0/Tumor Necrosis Factor-alpha; 10102-43-9/Nitric Oxide; 1190-74-5/2-mercaptoethylguanidine; 26404-66-0/peroxynitric acid; 50-02-2/Dexamethasone; 82115-62-6/Interferon-gamma; EC 1.14.13.39/Nitric Oxide Synthase; EC 1.14.13.39/Nitric Oxide Synthase Type II; EC 1.14.13.39/Nos2 protein, rat

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


Previous Document:  Estrogens modulate bovine vascular endothelial cell permeability and HSP 25 expression concomitantly...
Next Document:  Signal transduction in activation of ischemically sensitive abdominal visceral afferents: role of PK...