| Autor: |
Hofmann U; Department of Medicine/Cardiology, University of Würzburg, Germany., Domeier E, Frantz S, Laser M, Weckler B, Kuhlencordt P, Heuer S, Keweloh B, Ertl G, Bonz AW |
| Jazyk: |
angličtina |
| Zdroj: |
American journal of physiology. Heart and circulatory physiology [Am J Physiol Heart Circ Physiol] 2003 Jun; Vol. 284 (6), pp. H2100-5. Date of Electronic Publication: 2003 Jan 30. |
| DOI: |
10.1152/ajpheart.00888.2002 |
| Abstrakt: |
The present study investigated the effect of tumor necrosis factor (TNF)-alpha on myocardial energy metabolism as estimated by myocardial oxygen consumption (MVo(2)). MVo(2) of electrically stimulated isolated trabeculae of right ventricular Wistar rat myocardium was analyzed using a Clark-type oxygen probe. After the initial data collection in the absence of TNF-alpha, measurements were repeated after TNF-alpha stimulation. In separate experiments, pretreatment with the nitric oxide (NO) synthase inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME) or the ceramidase inhibitor n-oleoylethanolamine (NOE) was done to investigate NO/sphingosine-related effects. TNF-alpha impaired myocardial economy at increasing stimulation frequencies without altering baseline MVo(2). Incubation with TNF-alpha in the presence of l-NAME further impaired myocardial economy. NOE preincubation abrogated the TNF-alpha effect on myocardial economy. Moreover, the negative inotropic effect of TNF-alpha was observed in NOE-pretreated but not l-NAME-pretreated muscle fibers. Exogenous sphingosine mimicked the TNF-alpha effect on mechanics and energetics. We conclude that TNF-alpha impairs the economy of chemomechanical energy transduction primarily through a sphingosine-mediated pathway. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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