caa a22 4500 477118607 CHVBK 20180405111629.0 cr unu---uuuuu 170330e19960901xx s 000 0 eng 10.1007/BF00426336 doi (NATIONALLICENCE)springer-10.1007/BF00426336 Subchronic exposure of cardiomyocytes to low concentrations of tumor necrosis factor α attenuates the positive inotropic response not only to catecholamines but also to cardiac glycosides and high calcium concentrations [Elektronische Daten] [Peter Boekstegers, Iris Kainz, Wolfgang Giehrl, Wolfgang Peter, Karl Werdan] The main purpose of this study was to determine the subchronic effects of low concentrations of tumor necrosis factor α (TNFα) on the inotropic response and on the cellular level of high energy phosphates of cardiomyocytes. Therefore, the inotropic response of cultured neonatal rat heart cells to 10−5 M isoproterenol-, 10−6 M ouabain-, 10−5 M forskolin- and 2,4 mM calcium-perfusion was studied 24 h after exposure to TNFα (0.01/0.1/1/10/100 U/ml). In parallel experiments high energy phosphates (CP, ATP, ADP, AMP) were determined by high performance liquid chromatography. Furthermore, the reversibility of TNFα-induced changes was studied after washout of TNFα or after administration of anti-TNFα-antibody. Whereas control cells showed an increase of cell wall motion to 150 ± 5% of baseline value during 10-5 M isoproterenol-perfusion respectively 180 ± 7% during 2,4 mM calcium-perfusion, 24 h exposure of the cells to 1 U/ml up to 100 U/ml TNFα resulted in an inhibition of the inotropic response. Almost complete inhibition was observed 12 h after exposure to TNFα and was reversible 12 h after administration of the anti-TNFa-antibody. If the cells were perfused with 10−6 M ouabain or 10−5 M forskolin, a similar inhibition of the inotropic response was observed 24 h after TNFα-exposure. Determination of high energy phosphates showed that 24 h TNFα-exposure resulted in a reversible decrease of ATP, ADP, AMP and CP by 30-40% (p < 0.05). However, a similar reduction of cellular high energy phosphate levels using a TNFα independent mechanism (2,5 mM 2-deoxy-D-glucose) did not inhibit the inotropic response of the cardiomyocytes. From our results we conclude that subchronic exposure to low concentrations of TNFα resulted in an almost complete but reversible inhibition of the response of cardiomyocytes to different inotropic agents suggesting that a common final step of the inotropic cascade might be altered by TNFα. Though energy metabolism of TNFα exposed cells was affected also, reduction of high energy phosphate levels alone did not explain the observed inhibition of the inotropic response of the cardiomyocytes. Kluwer Academic Publishers, 1996 TNF nationallicence cardiomyocytes nationallicence inotropic response nationallicence high energy phosphates nationallicence Boekstegers Peter Department of Internal Medicine I, Klinikum Grofßhadern, University of Munich, Germany aut Kainz Iris Department of Internal Medicine I, Klinikum Grofßhadern, University of Munich, Germany aut Giehrl Wolfgang Department of Internal Medicine I, Klinikum Grofßhadern, University of Munich, Germany aut Peter Wolfgang Department of Internal Medicine I, Klinikum Grofßhadern, University of Munich, Germany aut Werdan Karl Department of Internal Medicine I, Klinikum Grofßhadern, University of Munich, Germany aut Molecular and Cellular Biochemistry Kluwer Academic Publishers 156/2(1996-09-01), 135-143 0300-8177 156:2<135 1996 156 11010 https://doi.org/10.1007/BF00426336 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00426336 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Boekstegers Peter Department of Internal Medicine I, Klinikum Grofßhadern, University of Munich, Germany aut NATIONALLICENCE 700 1- Kainz Iris Department of Internal Medicine I, Klinikum Grofßhadern, University of Munich, Germany aut NATIONALLICENCE 700 1- Giehrl Wolfgang Department of Internal Medicine I, Klinikum Grofßhadern, University of Munich, Germany aut NATIONALLICENCE 700 1- Peter Wolfgang Department of Internal Medicine I, Klinikum Grofßhadern, University of Munich, Germany aut NATIONALLICENCE 700 1- Werdan Karl Department of Internal Medicine I, Klinikum Grofßhadern, University of Munich, Germany aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Kluwer Academic Publishers 156/2(1996-09-01), 135-143 0300-8177 156:2<135 1996 156 11010 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer