Comparison of Terbutaline and Dobutamine in Rats with Endotoxemia

Jeng-Yuan Wu；Wen-Jinn Liaw；Chin Tzao；Shiu-Jen Chen；Jih-Hsin Wang；Chin-Chen Wu

tumor necrosis factor-α ； nitric oxide ； superoxide anion ； terbutaline ； dobutamine ； lipopolysaccharide

The Chinese Journal of Physiology

45卷4期（2002 / 12 / 31）

155 - 162

英文

It is generally accepted that bacterial endotoxin (lipopolysaccharide, LPS) acts via endogenous mediators leading to endotoxicity. Among these endogenous mediators, tumor necrosis factor-α(TNF-α) seems to induce all characteristics for endotoxemia. Inhibition of TNF-α production by cAMP- elevating agents has been well documented. Terbutaline (an agonist of β2-adrenoceptor) and dobutamine (an agonist of β1-adrenoceptor), both are able to increase intracellular cAMP via activation of adenylate cyclase, were examined in the anesthetized rat with endotoxemia. Terbutaline or dobutamine was administered to the rat at 30 mm after LPS injection. Hemodynamic changes and plasma TNF-α and nitrate (the end product of nitric oxide [NO]) levels as well as superoxide anion (O2•(superscript -)) production in the aorta were examined in this study. Results showed that terbutaline, but not dobutainine, improved the circulatory failure (e.g. hypotension and vascular hyporeactivity) in rats with endotoxemia. In addition, both terbittaline and dobutamine reduced the plasma TNF-α level, but only terbutaline attenuated the aortic O2•(superscript -) production in these endotoxemic rats. The beneficial effect of terbutaline in endotoxeniic animals was associated with a reduction in plasma TNF-α and aortic O2•(superscript -), but not in plasma NO.

1. Altura, B.M.,Lefer, A.M.,Schumer, W.(1983).Handbook of Shock and Trauma.Basic Science. NY:Raven Press.
2. Amezcua, J.L.,Palmer, R.M.,de Souza, B.M.,Moncada, S.(1989).Nitric oxide synthesized from L-arginine regulates vascular tone in the coronary circulation of the rabbit.Br. J. Pharmacol.,97,1119-1124.
3. Arai, T.,Hiromatsu, K.,Kobayashi, N.,Takano, M.,Ishida, H.,Nimura, Y.,Yoshikai, Y.(1995).IL-10 is invotved in the protective effect of dibutyl cyclic adenosine monophosphate on endotoxininduced inflammatory liver injury.J. Immunol.,155,5743-5749.
4. Beam, A.G.,Billing, B.,Sherlock, S.(1951).The effect of adrenaline and noradrenaline on hepatic blood flow and splanchnic carbohydrate metabolism in man.J. Physiol.,115,430-441.
5. Beck, G.C.,Oberacker, R.,Kapper, S.,von Zabem, D.,Schulte, J.,van Ackem, K.,van der Woude, F.J.,Yard, BA.(2001).Modulation of chemokine production in lung microvascular endothelial cells by dopamine is mediated via an oxidative mechanism.Am. J. Respir. Cell Mol. Biol.,25,636-643.
6. Beckman, J.S.,Beckman, T.W.,Chen, J.,Marshall, P.A.,Freeman, B.A.(1990).Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide.Proc. Natl. Acad. Sci. USA,87,1620-1624.
7. Beutler, B.,Cerami, A.(1989).The biology of cachectin/TNFα: a primary mediator of the host response.Ann. Rev. Immunol.,7,625-655.
8. Chu, A.,Chambers, D.E.,Lin, C.C.,Kuehl, W.D.,Palmer, R.M.,Moncada, S.(1991).Effects of inhibition of nitric oxide formation on basal vasomotion and endothelium-dependent responses of the coronary arteries in awake dog.J. Clin. Invest.,87,1964-1968.
9. Deitsch, E.A.(1992).Multiple organ failure: pathophysiology and potential future therapy.Ann Surg,216,117-134.
10. Hasko, G.,Szabo, C.,Nemeth, Z.H.,Kvetan, V.,Pastores, S.M.,vizi, E.S.(1996).Adenosine receptor agoniats differentially regulate IL-10 and TNF production in endotoxemic mice.J. Immunol.,157,4634-4640.
11. Hasko, G.,Szabo, C.,Nemeth, Z.H.,Salzman, A.L.,Vizi, E.S.(1998).Stimulation of β-adrenoceptors inhibits endotoxin-induced IL-12 production in normal and IL-10 deficient mice.J. Neuroimmunol.,88,57-61.
12. Hayes, M.A.,Timmins, A.C.,Yau, E.H.,Palazzo, M.,Hinds, C.J.,Watson, D.(1994).Elevation of systemic oxygen delivery in the treatment of critically ill patients.N. EngL J. Med.,330,1717-1722.
13. Hoffman, B.B.,Lefkowitz, R.J.,Hardman, J.G.,Limbird, L.E.,Molinoff, P.B.,Ruddon, R.W.,Gilman, A.G. (eds)(1996).Catecholamines, sympathomimetic drugs, and adrenergic receptor antagonists.Goodman & Gilman`s The Pharmacological Basis of Therapeutics,199-248.
14. Kavelaars, A.,van de Pol, M.,Zijlstra, J.,Heijnen, C.J.(1997).β2-Adrenergic activation enhances interleukin-8 production by human monocytes.J. Neuroimmunol.,77,211-216.
15. Liao, M.H.,Wu, C.C.(2000).Effects of dobutamine on circulatory failure and survival in rats with endotoxemia.J. Med. Sci.,20,416-428.
16. Lipton, S.A.,Choi, Y.B.,Pan, Z.H.,Lei, S.Z.,Chen, H.S.,Sucher, N.J.,Loscalzo, J.,Singel, D.J.,Stamler, J.S.(1993).A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds.Nature (London),364,626-632.
17. Macarthur, H.,Westfall, T.C.,Riley, D.P.,Misko, T.P.,Salvemini, D.(2000).Inactivation of catecholamines by superoxide gives new insights on the pathogenesis of septic shock.Proc. Natl. Acad. Sci. U.S.A.,97,9753-9758.
18. McLean, J.S.,Byrick, R.J.(1993).ARDS and sepsis-definitions and new therapy.Can. J. Anesth.,40,585-590.
19. Metcalf, K.,Jungersten, L.,Lisander, B.(2002).Effective inhibition of nitric oxide by aminoguanidine does not reverse hypotension in endotoxemic rats.Acta Aoaesthesiol. Scand.,46,17-23.
20. Mira, J.P.,Fabre, J.E.,Baigorri, F.,Coste, J.,Annat, G.,Artigas, A.,Nitenberg, G.,Dhainaut, J.F.(1994).Lack of oxygen supply dependency in patients with severe sepsis. A study of oxygen delivery increase by military antishock trouser and dobutamine.Chess,106,1524-1531.
21. Moncada, S.,Palmer, R.M.J.,Higgs, E.A.(1991).Nitric oxide: Physiology, pathophysiology and pharmacology.Phormacol. Rev.,43,109-142.
22. Nathan, C.,Xie, Q.W.(1994).Regulation of biosynthesis of nitric oxide.J. Biol. Chem.,269,13725-13728.
23. Nathan, C.F.(1987).Secretory products of maerophages.J. Clin. Invest.,79,319-326.
24. Panina-Bordignon, P.,Mazzeo, D.,Di Lucia, P.,D`Ambrosio, D.,Lang, R.,Fabbri, L.,Self, C.,Sinigaglia, F.(1997).β2-Agonists prevent Th1 development by selective inhibition of interleukin 12.J. Clin. Invest.,100,1513-1519.
25. Parker, M.M.,Shelhamer, J.H.,Natanson, C.,Alling, D.,Parillo, J.E.(1987).Seroa hemodynamic patterns in survivors and non-survivors of septic shock in humans.Crit. Care Med.,15,923-929.
26. Phang, P.T.,Cunningham, K.F.,Ronco, J.J.,Wiggs, B.R.,Russell, J.A.(1994).Mathematical coupling explains dependence of oxygen delivery in ARDS.Am. J. Respir. Crit. Core Med.,150,318-323.
27. Platzer, C.,Meisel, C.,Vogt, K.,Platzer, M.,Volk, H.D.(1994).Up- regulation of monocytie IL-10 by tumor necrosis factor-a and cAMP elevating drugs.Int. Immunol.,7,517-523.
28. Reinelt, H.,Radermacher, P.,Fischer, G.,Geisser, W.,Trunk, E.,Wiedeck, H.,Mezody, M.,Georgieff, M.,Vogt, J.(1997).Dobutamine and dopexamine and the splanchnic metabolic response in septic shock.Clin. Intens. Care,8,38-41.
29. Repine, J.E.(1992).Scientific perspectives on adult respiratory distress syndrome.Lancet,339,466-469.
30. Severn, A.,Rapson, N.T.,Hunter, C.A.,Liew, F.Y.(1992).Regulation of tumor necrosis factor production by adrenaline and beta-adrenergic agonists.J. Immunol.,148,3441-3445.
31. Shoemaker, W.C.,Appel, P.L.,Kram, H.B.(1986).Hemodynamic and oxygen transport effects of dobutamine in critically ill general surgical patients.Crit. Care Med.,14,1032-1037.
32. Silverman, H.J.,Penaranda, R.,Orens, J.B.,Lee, N.H.(1993).Impaired beta-adrenergic receptor stimulation of cyclic adenosine mono-phosphate in human septic shock: association with myocardial hyporesponsiveness to catecholamines.Crit. Care Med.,21,31-39.
33. Stoclet, J.C.,Fleming, I.,Gray, G.,Julou-Sehaeffer, G.,Schneider, F.,Schott, C.,Sehott, C.,Parratt, J.R.(1993).Nitric oxide and endotoxemia.Circulation,87,77-80.
34. Strassmann, G.,Patil-Koota, V.,Finkelman, F.,Fong, M.,Kambayashi, T.(1994).Evidence for the involvement of interleukin 10 in the differential deactivation of murine peritoneal macrophages by prostaglandin E2.J. Exp. Med.,180,2365-2370.
35. Sugino, K.,Dohi, K.,Yamada, K.,Kawasaki, T.(1989).Changes in the levels of endogenous antioxidants in the liver of mice with experimental endotoxemia and the protective effects of the antioxidants.Surgery,105,200-206.
36. Szabo, C.(1995).Alterations in nitric oxide production in various forms of circulatory shock.New Horizons,3,2-32.
37. Szabo, C.,Hasko, G.,Zingarelli, B.,Nemeth, Z.H.,Salzman, A.L.,Kvetan, V.,Pastores, S.M.,Vizi, E.S.(1997).Isoproterenol regulates tumor necrosis factor, interleukin-10, interleukin-6 and nitric oxide production and protects against the development of vascular hyporeactivity in endotoxemia.Immunology,90,95-100.
38. Taffet, S.M.,Singhel, K.J.,Overholtzer, J.F.,Shurtleff, S.A.(1989).Regulation of tumor necrosis factor expression in a macrophage like cell line by lipopolysaceharide and cyclic AMP.Cell Immunol,120,291-300.
39. Thiemermann, C.(1994).The role of the L-arginine: nitric oxide pathway in circulatory shock.Adv. Pharmacol.,28,45-79.
40. Thiemermann, C.,Wu, C.C.,Szabo, C.,Perretti, M.,Vane, J.R.(1993).Role of tumor necrosis factor in the induction of nitric oxide synthase in a rat model of endotoxin shock.Br. J. Pharmacol.,110,177-182.
41. Tracey, K.J.,Cerami, A.(1993).Tumor necrosis factor, other cytokines and disease.Annu. Rev. Cell Biol.,9,317-343.
42. Vallet, B.,Curtis, S.E.,Chopin, C.(1995).Prognostic value of the dobutamine test in patients with sepsis syndrome: a prospective multicenter study.Crit. Care Med.,23,415-416.
43. Wu, C.C.,Chiao, C.W.,Hsiao, G.,Chen, A,Yen, M.H.(2001).Melatonin prevents endotoxin-induced circulatory failure in rats.J. Pineal Res.,30,147-156.
44. Wu, C.C.,Liao, M.H.,Chen, S.J.,Chou, T.C.,Chen, A.,Yen, M.H.(2000).Terbutaline prevents circulatory failure and mitigates mortality in rodents with endotoxemia.Shock,14,60-67.
45. Wu, C.C.,Liao, M.H.,Chen, S.J.,Yen, M.R.(1999).Pentoxifylline improves circulatory failure and survival in murine models of endotoxemia.Eur. J. Phormacol.,373,41-49.