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Norepinephrine-induced expression of cytokines in isolated biventricular working rat hearts

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Abstract

The norepinephrine (NE)-induced hypertrophy of the left ventricle (LV) in the rat is associated with increased interleukin (IL)-6 and IL-1β 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/dtmax) were lower. After NE infusion (30 nM), SP and dP/dtmax were increased by 30 and 90%, respectively, in both ventricles. In vivo, the ventricles showed a different response to NE (0.1 mg/kg·h): LVSP increased by 15%, RVSP and RV dP/dtmax was doubled, LV dP/dtmax was tripled. The analysis of cytokine mRNA expression with the RNase protection assay revealed that in vivo IL-6 and IL-1β were increased between 4 and 12 h 80- and 12-fold, respectively, while there was weak expression under control conditions. In the IBWH IL-1α, IL-1β, IL-6 and tumor necrosis factor (TNF)α 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.

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References

  1. Hirano T, Yasukawa K, Harada H, Taga T, Watanabe Y, Matsuda T, Kashiwamura S, Nakajima K, Koyama K, Iwamatsu A et al.: Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin. Nature 324: 73-76, 1986

    Google Scholar 

  2. Kishimoto T, Hirano T: Molecular regulation of B lymphocyte response. Annu Rev Immunol 6: 485-512, 1988

    Google Scholar 

  3. Kukielka GL, Smith CW, Manning AM, Youker KA, Michael LH, Entman ML: Induction of interleukin-6 synthesis in the myocardium. Potential role in postreperfusion inflammatory injury. Circulation 92: 1866-1875, 1995

    Google Scholar 

  4. Natanson C, Eichenholz PW, Danner RL, Eichacker PQ, Hoffman WD, Kuo GC, Banks SM, MacVittie TJ, Parrillo JE: Endotoxin and tumor necrosis factor challenges in dogs simulate the cardiovascular profile of human septic shock. J Exp Med 169: 823-832, 1989

    Google Scholar 

  5. Pagani FD, Baker LS, Hsi C, Knox M, Fink MP, Visner MS: Left ventricular systolic and diastolic dysfunction after infusion of tumor necrosis factor-alpha in conscious dogs. J Clin Invest 90: 389-398, 1992

    Google Scholar 

  6. Finkel MS, Oddis CV, Jacob TD, Watkins SC, Hattler BG, Simmons RL: Negative inotropic effects of cytokines on the heart mediated by nitric oxide. Science 257: 387-389, 1992

    Google Scholar 

  7. Yokoyama T, Vaca L, Rossen RD, Durante W, Hazarika P, Mann DL: Cellular basis for the negative inotropic effects of tumor necrosis factor-alpha in the adult mammalian heart. J Clin Invest 92: 2303-2312, 1993

    Google Scholar 

  8. Fowler MB, Laser JA, Hopkins GL, Minobe W, Bristow MR: Assessment of the beta-adrenergic receptor pathway in the intact failing human heart: Progressive receptor down-regulation and subsensitivity to agonist response. Circulation 74: 1290-1302, 1986

    Google Scholar 

  9. Gulick T, Chung MK, Pieper SJ, Lange LG, Schreiner GF: Interleukin 1 and tumor necrosis factor inhibit cardiac myocyte beta-adrenergic responsiveness. Proc Natl Acad Sci USA 86: 6753-6757, 1989

    Google Scholar 

  10. Pedersen BK, Steensberg A, Schjerling P: Muscle-derived interleukin-6: Possible biological effects. J Physiol 536: 329-337, 2001

    Google Scholar 

  11. Rehman J, Mills PJ, Carter SM, Chou J, Thomas J, Maisel AS: Dynamic exercise leads to an increase in circulating ICAM-1: Further evidence for adrenergic modulation of cell adhesion. Brain Behav Immun 11: 343-351, 1997

    Google Scholar 

  12. Munger MA, Johnson B, Amber IJ, Callahan KS, Gilbert EM: Circulating concentrations of proinflammatory cytokines in mild or moderate heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol 77: 723-727, 1996

    Google Scholar 

  13. Wollert KC, Drexler H: The role of interleukin-6 in the failing heart. Heart Fail Rev 6: 95-103, 2001

    Google Scholar 

  14. Ono K, Matsumori A, Shioi T, Furukawa Y, Sasayama S: Cytokine gene expression after myocardial infarction in rat hearts: Possible implication in left ventricular remodeling. Circulation 98: 149-156, 1998

    Google Scholar 

  15. Prabhu SD, Chandrasekar B, Murray DR, Freeman GL: Beta-adrenergic blockade in developing heart failure: Effects on myocardial inflammatory cytokines, nitric oxide, and remodeling. Circulation 101: 2103-2109, 2000

    Google Scholar 

  16. Deten A, Volz HC, Briest W, Zimmer H-G: Cardiac cytokine expression is upregulated in the acute phase after myocardial infarction. Experimental studies in rats. Cardiovasc Res 55: 329-340, 2002

    Google Scholar 

  17. Hirota H, Yoshida K, Kishimoto T, Taga T: Continuous activation of gp130, a signal-transducing receptor component for interleukin 6-related cytokines, causes myocardial hypertrophy in mice. Proc Natl Acad Sci USA 92: 4862-4866, 1995

    Google Scholar 

  18. Pan J, Fukuda K, Kodama H, Sano M, Takahashi T, Makino S, Kato T, Manabe T, Hori S, Ogawa S: Involvement of gp130-mediated signaling in pressure overload-induced activation of the JAK/STAT pathway in rodent heart. Heart Vessels 13: 199-208, 1998

    Google Scholar 

  19. Barth W, Deten A, Bauer M, Reinohs M, Leicht M, Zimmer H-G: Differential remodeling of the left and right heart after norepinephrine treatment in rats: Studies on cytokines and collagen. J Mol Cell Cardiol 32: 273-284, 2000

    Google Scholar 

  20. Müller-Strahl GH, Hemker J, Zimmer H-G: Comparison between left and right heart function in the isolated biventricular working rat heart. Exp Clin Cardiol 7: 7-19, 2002

    Google Scholar 

  21. Zimmer H-G: Measurement of left ventricular hemodynamic parameters in closed-chest rats under control and various pathophysiologic conditions. Basic Res Cardiol 78: 77-84, 1983

    Google Scholar 

  22. Zimmer H-G, Zierhut W, Seesko RC, Varekamp AE: Right heart catheterization in rats with pulmonary hypertension and right ventricular hypertrophy. Basic Res Cardiol 83: 48-57, 1988

    Google Scholar 

  23. Bünger R, Haddy FJ, Querengässer A, Gerlach E: An isolated guinea pig heart preparation with in vivo like features. Pflügers Arch 353: 317-326, 1975

    Google Scholar 

  24. Taegtmeyer H, Hems R, Krebs HA: Utilization of energy-providing substrates in the isolated working rat heart. Biochem J 186: 701-711, 1980

    Google Scholar 

  25. Westerhof N, Elzinga G, Sipkema P: An artificial arterial system for pumping hearts. J Appl Physiol 31: 776-781, 1971

    Google Scholar 

  26. Raßler B, Barth W, Zimmer H-G: Transient pleural effusion in norepinephrine-stimulated rats. Basic Res Cardiol 96: 471-477, 2001

    Google Scholar 

  27. Chomczynski P, Sacchi N: Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162: 156-159, 1987

    Google Scholar 

  28. Bürger A, Benicke M, Deten A, Zimmer H-G: Catecholamines stimulate interleukin-6 synthesis in rat cardiac fibroblasts. Am J Physiol Heart Circ Physiol 281: H14-H21, 2001

    Google Scholar 

  29. Church GM, Gilbert W: Genomic sequencing. Proc Natl Acad Sci USA 81: 1991-1995, 1984

    Google Scholar 

  30. Northemann W, Braciak TA, Hattori M, Lee F, Fey GH: Structure of the rat interleukin 6 gene and its expression in macrophage-derived cells. J Biol Chem 264: 16072-16082, 1989

    Google Scholar 

  31. Demmy TL, Magovern GJ, Kao RL: Isolated biventricular working rat heart preparation. Ann Thorac Surg 54: 915-920, 1992

    Google Scholar 

  32. Paterson DJ, Blake GJ, Leitch SP, Phillips SM, Brown HF: Effects of catecholamines and potassium on cardiovascular performance in the rabbit. J Appl Physiol 73: 1413-1418, 1992

    Google Scholar 

  33. Waldenström A, Martinussen HJ, Kock J, Ronquist G, Hultman J: Parasympathetic muscarinic stimulation limits noradrenaline induced myocardial creatine kinase release: A study in the isolated perfused working rat heart. Scand J Clin Lab Invest 54: 615-621, 1994

    Google Scholar 

  34. Kapadia S, Lee J, Torre-Amione G, Birdsall HH, Ma TS, Mann DL: Tumor necrosis factor-alpha gene and protein expression in adult feline myocardium after endotoxin administration. J Clin Invest 96: 1042-1052, 1995

    Google Scholar 

  35. Mann DL: Stress activated cytokines and the heart. Cytokine Growth Factor Rev 7: 341-354, 1996

    Google Scholar 

  36. Löw-Friedrich I, Weisensee D, Mitrou P, Schoeppe W: Cytokines induce stress protein formation in cultured cardiac myocytes. Basic Res Cardiol 87: 12-18, 1992

    Google Scholar 

  37. Palmieri EA, Benincasa G, Di Rella F, Casaburi C, Monti MG, De Simone G, Chiariotti L, Palombini L, Bruni CB, Sacca L, Cittadini A: Differential expression of TNF-alpha, IL-6, and IGF-1 by graded mechanical stress in normal rat myocardium. Am J Physiol Heart Circ Physiol 282: H926-H934, 2002

    Google Scholar 

  38. Choi I, Kang HS, Yang Y, Pyun KH: IL-6 induces hepatic inflammation and collagen synthesis in vivo. Clin Exp Immunol 95: 530-535, 1994

    Google Scholar 

  39. Briest W, Hölzl A, Rassler B, Deten A, Leicht M, Baba HA, Zimmer HG: Cardiac remodeling after long term norepinephrine treatment in rats. Cardiovasc Res 52: 265-273, 2001

    Google Scholar 

  40. Kondo K, Okada T, Matsui T, Kato S, Date K, Yoshihara M, Nagata Y, Takagi H, Yoneda M, Sugie I: Establishment and characterization of a human B cell line from the lung tissue of a patient with scleroderma; extraordinary high level of IL-6 secretion by stimulated fibroblasts. Cytokine 13: 220-226, 2001

    Google Scholar 

  41. Xue H, McCauley RL, Zhang W: Elevated interleukin-6 expression in keloid fibroblasts. J Surg Res 89: 74-77, 2000

    Google Scholar 

  42. Yue P, Massie BM, Simpson PC, Long CS: Cytokine expression increases in nonmyocytes from rats with postinfarction heart failure. Am J Physiol 275: H250-H258, 1998

    Google Scholar 

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Authors and Affiliations

  1. Carl-Ludwig-Institute of Physiology, University of Leipzig, Liebigstrasse 27, D-04103, Leipzig, Germany

    Wilfried Briest, Christian Elsner, Jan Hemker, Gerhard Müller-Strahl & Heinz-Gerd Zimmer

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  1. Wilfried Briest
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  2. Christian Elsner
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  3. Jan Hemker
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  4. Gerhard Müller-Strahl
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  5. Heinz-Gerd Zimmer
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Briest, W., Elsner, C., Hemker, J. et al. Norepinephrine-induced expression of cytokines in isolated biventricular working rat hearts. Mol Cell Biochem 245, 69–76 (2003). https://doi.org/10.1023/A:1022861609896

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