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PMID: 10051135 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Effects of tumour necrosis factor-alpha on left ventricular function in the rat isolated perfused heart: possible mechanisms for a decline in cardiac function.

British journal of pharmacology ·Vol. 126 ·No. 1 ·1999-01-00 ·Pages 189-96

Edmunds NJ, Lal H, Woodward B

Abstract

1. The cardiac depressant actions of TNF were investigated in the isolated perfused rat heart under constant flow (10 ml min(-1)) and constant pressure (70 mmHg) conditions, using a recirculating (50 ml) mode of perfusion. 2. Under constant flow conditions TNF (20 ng ml(-1)) caused an early (< 25 min) decrease in left ventricular developed pressure (LVDP), which was maintained for 90 min (LVDP after 90 min: control vs TNF; 110 +/- 4 vs 82 +/- 10 mmHg, P < 0.01). 3. The depression in cardiac function seen with TNF under constant flow conditions, was blocked by the ceramidase inhibitor N-oleoylethanolamine (NOE), 1 microM, (LVDP after 90 min: TNF vs TNF with NOE; 82 +/- 10 vs 11 +/- 5 mmHg, P < 0.05). 4. In hearts perfused at constant pressure, TNF caused a decrease in coronary flow rate (change in flow 20 min after TNF: control vs TNF; -3.0 +/- 0.9 vs -8.7 +/- 1.2 ml min(-1), P < 0.01). This was paralleled by a negative inotropic effect (change in LVDP 20 min after TNF: control vs TNF; -17 +/- 7 vs -46 +/- 6 mmHg, P < 0.01). The decline in function was more rapid and more severe than that seen under conditions of constant flow. 5. These data indicate that cardiac function can be disrupted by TNF on two levels, firstly via a direct, ceramidase dependant negative inotropic effect, and secondly via an indirect coronary vasoconstriction.

MeSH Terms
Animals Antihypertensive Agents/pharmacology Bosentan Endocannabinoids Endothelin Receptor Antagonists Endothelin-1/pharmacology Enzyme Inhibitors/pharmacology Ethanolamines/pharmacology Heart/drug effects,physiology Heart Rate/drug effects Heart Ventricles/drug effects In Vitro Techniques Indomethacin/pharmacology Male Myocardial Contraction/drug effects Nitroarginine/pharmacology Oleic Acids Perfusion Pressure Rats Rats, Wistar Sphingomyelin Phosphodiesterase/pharmacology Stroke Volume/drug effects,physiology Sulfonamides/pharmacology Temperature Tumor Necrosis Factor-alpha/pharmacology Ventricular Function Ventricular Function, Left/drug effects
Chemicals
Antihypertensive Agents Endocannabinoids Endothelin Receptor Antagonists Endothelin-1 Enzyme Inhibitors Ethanolamines Oleic Acids Sulfonamides Tumor Necrosis Factor-alpha N-oleoylethanolamine Nitroarginine Sphingomyelin Phosphodiesterase Bosentan Indomethacin
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Edmunds N J
Department of Pharmacology, University of Bath, Claverton Down.
Lal H
Woodward B
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Article Info
Journal
British journal of pharmacology
Abbr.
Br J Pharmacol
ISSN
0007-1188
DOI
10.1038/sj.bjp.0702294
Published
1999-01-00
Pages
189-96
Language
English
Region
England
NLM ID
7502536
PMCID
PMC1565798
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.bjp.0702294 PMC Full Text View journal details
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