PMID- 12708746 OWN - NLM STAT- MEDLINE DCOM- 20040114 LR - 20190818 IS - 0300-8177 (Print) IS - 0300-8177 (Linking) VI - 245 IP - 1-2 DP - 2003 Mar TI - Norepinephrine-induced expression of cytokines in isolated biventricular working rat hearts. PG - 69-76 AB - The norepinephrine (NE)-induced hypertrophy of the left ventricle (LV) in the rat is associated with increased interleukin (IL)-6 and IL-1beta expression. In the present study, a newly established model of isolated biventricular working rat heart was used to examine whether NE may directly induce cytokine mRNA expression in a preparation devoid of other circulating hormonal and humoral factors. Representative hemodynamic parameters and the expression of various cytokines of the isolated biventricular working heart (IBWH) were compared with the respective in vivo results. Systolic pressure (SP) of the right ventricle (RVSP) was higher in the IBWH than in the intact anesthetized rat (42.9 +/- 1.89 vs. 32.3 +/- 1.06). However, heart rate (HR), LVSP and the maximal rate of pressure development of LV (LV dP/dt(max)) were lower. After NE infusion (30 nM), SP and dP/dt(max) were increased by 30 and 90%, respectively, in both ventricles. In vivo, the ventricles showed a different response to NE (0.1 mg/kg x h): LVSP increased by 15%, RVSP and RV dP/dt(max) was doubled, LV dP/dt(max) was tripled. The analysis of cytokine mRNA expression with the RNase protection assay revealed that in vivo IL-6 and IL-1beta were increased between 4 and 12 h 80- and 12-fold, respectively, while there was weak expression under control conditions. In the IBWH IL- 1alpha, IL-1beta, IL-6 and tumor necrosis factor (TNF)alpha were increased already during control perfusion. The increase of these stress-activated cytokines indicates that the isolation and perfusion procedure may exert a stress on the heart. NE induced an additional time-dependent increase of IL-6 mRNA after 1 h of infusion. Thus, NE has a direct effect on the cardiac IL-6 expression, which occurred earlier in the in vitro preparation than in the rat heart in vivo. FAU - Briest, Wilfried AU - Briest W AD - Carl-Ludwig-Institute of Physiology, University of Leipzig, Leipzig, Germany. briestw@medizin.uni-leipzig.de FAU - Elsner, Christian AU - Elsner C FAU - Hemker, Jan AU - Hemker J FAU - Muller-Strahl, Gerhard AU - Muller-Strahl G FAU - Zimmer, Heinz-Gerd AU - Zimmer HG LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Mol Cell Biochem JT - Molecular and cellular biochemistry JID - 0364456 RN - 0 (Cytokines) RN - 0 (Interleukin-1) RN - 0 (Interleukin-6) RN - 0 (Tumor Necrosis Factor-alpha) RN - X4W3ENH1CV (Norepinephrine) SB - IM MH - Animals MH - Cytokines/drug effects/genetics/*metabolism MH - Female MH - Gene Expression Regulation/*drug effects MH - Heart/*drug effects MH - Heart Rate/drug effects MH - Heart Ventricles/drug effects MH - Interleukin-1/genetics/metabolism MH - Interleukin-6/genetics/metabolism MH - Myocardial Contraction/*drug effects/*physiology MH - Norepinephrine/*pharmacology MH - Rats MH - Rats, Sprague-Dawley MH - Rats, Wistar MH - Tumor Necrosis Factor-alpha/genetics/metabolism EDAT- 2003/04/24 05:00 MHDA- 2004/01/15 05:00 CRDT- 2003/04/24 05:00 PHST- 2003/04/24 05:00 [pubmed] PHST- 2004/01/15 05:00 [medline] PHST- 2003/04/24 05:00 [entrez] AID - 10.1023/a:1022861609896 [doi] PST - ppublish SO - Mol Cell Biochem. 2003 Mar;245(1-2):69-76. doi: 10.1023/a:1022861609896.