Induction of Vasoactive Substances Differs in LPS-Induced and TF-Induced DIC Models in Rats

 

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Summary

We have investigated the role of two vasoactive substances, nitric oxide (NO) and endothelin (ET), in the pathophysiology of disseminated intravascular coagulation (DIC), using two types of DIC models. Experimental DIC was induced by sustained infusion of 0.1, 1, 10, or 50 mg/kg lipopolysaccharide (LPS), or 3.75 U/kg thromboplastin (TF), for 4 h via the rat tail vein. Plasma levels of both NOX (metabolites of NO) and ET were significantly increased following infusion of 0.1 mg/kg or greater of LPS in the LPS-induced DIC rat model. In contrast, although a marked increase in the plasma levels of NOX was observed, only a slight increase in plasma ET levels was seen in the TF-induced DIC rat model. No significant differences in the plasma levels of platelets or thrombin-ATIII complex were observed among the TF-induced and LPS (50 mg/dl)-induced DIC models. However, plasma NOX levels rose significantly higher in the TF-induced model, relative to the LPS-induced model (p <0.01). Conversely, plasma ET levels were significantly greater after LPS-induction, compared to TF-induction, of DIC (p <0.01). Vasoconstriction, as well as depressed fibrinolytic activity, may be additional factors leading to severe organ dysfunction in the LPS-induced DIC rat model. Moreover, vasodilatation, as well as enhanced fibrinolytic activity, may help to prevent rats from severe organ dysfunction in the TF-induced DIC model. Our results suggest that modulator of vasoactive substances should be examined in the treatment of DIC.

• References

• 1 Paloma MJ, Paramo JA, Rocha E. Endotoxin-induced intravascular coagulation in rabbits: effect of tissue plasminogen activator vs. urokinase of PAI generation, fibrin deposits and mortality. Thromb Haemost 1995; 74: 1578-82.
  Article in Thieme ConnectPubMedGoogle Scholar
• 2 Munoz MC, Montes R, Hermida J, Orbe J, Paramo JA, Rocha E. Effect of the administration of recombinant hirudin and/or tissue plasminogen activator (t-PA) on endotoxin-induced disseminated intravascular coagulation model in rabbits. Br J Haematol 1999; 105: 117-21.
  CrossrefPubMedGoogle Scholar
• 3 Asakura H, Ontachi Y, Mizutani T, Kato M, Saito M, Kumabashiri I, Morishita E, Yamazaki M, Aoshima K, Nakao S. An enhanced fibrinolysis prevents the development of multiple organ failure in disseminated intravascular coagulation in spite of much activation of blood coagulation. Crit Care Med 2001; 29: 1164-8.
  CrossrefPubMedGoogle Scholar
• 4 Feinstein DI. Diagnosis and management of disseminated intravascular coagulation: the role of heparin therapy. Blood 1982; 60: 284-7.
  PubMedGoogle Scholar
• 5 Sakata Y, Yoshida N, Matsuda M, Aoki N. Treatment of DIC with antithrombin III concentrates. Bibl Haematol 1983; 49: 307-16.
  PubMedGoogle Scholar
• 6 Rubin RN, Colman RW. Disseminated intravascular coagulation. Approach to treatment. Drugs 1992; 44: 963-71.
  CrossrefPubMedGoogle Scholar
• 7 Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y, Yazaki Y, Goto K, Masaki T. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 1988; 332: 411-5.
  CrossrefPubMedGoogle Scholar
• 8 Yanagisawa M, Inoue A, Ishikawa T, Kasuya Y, Kimura S, Kumagaye S, Nakajima K, Watanabe TX, Sakakibara S, Goto K. et al. Primary structure, synthesis, and biological activity of rat endothelin, an endothelium-derived vasoconstrictor peptide. Proc Natl Acad Sci USA 1988; 85: 6964-7.
  CrossrefPubMedGoogle Scholar
• 9 Shichiri M, Hirata Y, Ando K, Emori T, Ohta K, Kimoto S, Ogura M, Inoue A, Marumo F. Plasma endothelin levels in hypertension and chronic renal failure. Hypertension 1990; 15: 493-6.
  CrossrefPubMedGoogle Scholar
• 10 Watanabe T, Suzuki N, Shimamoto N, Fujino M, Imada A. Contribution of endogenous endothelin to the extension of myocardial infarct size in rats. Circ Res 1991; 69: 370-7.
  CrossrefPubMedGoogle Scholar
• 11 Hartikainen-Sorri AL, Vuolteenaho O, Leppaluoto J, Ruskoaho H. Endothelin in umbilical artery vasospasm. Lancet 1991; 337: 619.
  CrossrefPubMedGoogle Scholar
• 12 Zeiher AM, Goebel H, Schachinger V, Ihling C. Tissue endothelin-1 immunoreactivity in the active coronary atherosclerotic plaque. A clue to the mechanism of increased vasoreactivity of the culprit lesion in unstable angina. Circulation 1995; 91: 941-7.
  CrossrefPubMedGoogle Scholar
• 13 Ishibashi M, Saito K, Watanobe K, Uesugi S, Furue H, Yamaji T. Plasma endothelin-1 levels in patients with disseminated intravascular coagulation. N Engl J Med 1991; 324: 1516-7.
  CrossrefPubMedGoogle Scholar
• 14 Asakura H, Jokaji H, Saito M, Uotani C, Kumabashiri I, Morishita E, Yamazaki M, Matsuda T. Role of endothelin in disseminated intravascular coagulation. Am J Hematol 1992; 41: 71-5.
  CrossrefPubMedGoogle Scholar
• 15 Forstermann U, Boissel JP, Kleinert H. Expressional control of the “constitutive” isoforms of nitric oxide synthase (NOS I and NOS III). FASEB J 1998; 12: 773-90.
  CrossrefPubMedGoogle Scholar
• 16 Geller DA, Billiar TR. Molecular biology of nitric oxide synthases. Cancer Metastasis Rev 1998; 17: 7-23.
  CrossrefPubMedGoogle Scholar
• 17 Kroncke KD, Fehsel K, Kolb-Bachofen V. Inducible nitric oxide synthase in human diseases. Clin Exp Immunol 1998; 113: 147-56.
  CrossrefPubMedGoogle Scholar
• 18 Szabo C, Southan GJ, Thiemermann C. Beneficial effects and improved survival in rodent models of septic shock with S-methylisothiourea sulfate, a potent and selective inhibitor of inducible nitric oxide synthase. Proc Natl Acad Sci USA 1994; 91: 12472-6.
  CrossrefPubMedGoogle Scholar
• 19 Bouchie JL, Hansen H, Feener EP. Natriuretic factors and nitric oxide suppress plasminogen activator inhibitor-1 expression in vascular smooth muscle cells. Role of cGMP in the regulation of the plasminogen system. Arterioscler Thromb Vasc Biol 1998; 18: 1771-9.
  CrossrefPubMedGoogle Scholar
• 20 Gerlach M, Keh D, Bezold G, Spielmann S, Kurer I, Peter RU, Falke KJ, Gerlach H. Nitric oxide inhibits tissue factor synthesis, expression and activity in human monocytes by prior formation of peroxynitrite. Intensive Care Med 1998; 24: 1199-208.
  CrossrefPubMedGoogle Scholar
• 21 Yang Y, Loscalzo J. Regulation of tissue factor expression in human microvascular endothelial cells by nitric oxide. Circulation 2000; 101: 2144-8.
  CrossrefPubMedGoogle Scholar
• 22 Ferreia HC, Murat LG. Immunological method for demonstrating fibrin degradation products in serum and its use in the diagnosis of fibrinolytic states. Br J Haematol 1963; 09: 299-310.
  CrossrefPubMedGoogle Scholar
• 23 Pelzer H, Schwarz A, Heimburger N. Determination of human thrombinantithrombin III complex in plasma with an enzyme-linked immunosorbent assay. Thromb Haemost 1988; 59: 101-6.
  Article in Thieme ConnectPubMedGoogle Scholar
• 24 Komatsu T, Saika K, Ogura K, Yamanaka S, Nishimori Y, Shimasaki M. Evaluation of ready-to-use, liquid type reagents for creatinine assay “L-type Wako Creatinine F”. J Clin Lab Inst Reag 1996; 19: 807-13.
  PubMedGoogle Scholar
• 25 Bergmeyer HU, Scheibe P, Wahlefeld AW. Optimization of methods for aspartate aminotransferase and alanine aminotransferase. Clin Chem 1978; 24: 58-73.
  PubMedGoogle Scholar
• 26 Nims RW, Cook JC, Krishna MC, Christodoulou D, Poore CM, Miles AM, Grisham MB, Wink DA. Colorimetric assays for nitric oxide and nitrogen oxide species formed from nitric oxide stock solutions and donor compounds. Methods Enzymol 1996; 268: 93-105.
  PubMedGoogle Scholar
• 27 Suzuki N, Matsumoto H, Kitada C, Masaki T, Fujino M. A sensitive sandwich-enzyme immunoassay for human endothelin. J Immunol Methods 1989; 118: 245-50.
  CrossrefPubMedGoogle Scholar
• 28 Kawasaki H, Hayashi K, Awai M. Disseminated intravascular coagulation (DIC). Immunohistochemical study of fibrin-related materials (FRMs) in renal tissues. Acta Pathol Jpn Jan 1987; 37: 77-84.
  PubMedGoogle Scholar
• 29 Okajima K, Sakamoto Y, Uchiba M. Heterogeneity in the incidence and clinical manifestations of disseminated intravascular coagulation: a study of 204 cases. Am J Hematol 2000; 65: 215-22.
  CrossrefPubMedGoogle Scholar
• 30 Asakura H, Suga Y, Aoshima K, Ontachi Y, Mizutani T, Kato M, Saito M, Morishita E, Yamazaki M, Takami A, Miyamoto K, Nakao S. Marked difference in pathophysiology between tissue factorand lipopolysaccharide-induced disseminated intravascular coagulation models in rats. Crit Care Med 2002; 30: 161-4.
  CrossrefPubMedGoogle Scholar
• 31 Walter R, Schaffner A, Schoedon G. Differential regulation of constitutive and inducible nitric oxide production by inflammatory stimuli in murine endothelial cells. Biochem Biophys Res Commun 1994; 202: 450-5.
  CrossrefPubMedGoogle Scholar
• 32 Kaddoura S, Curzen NP, Evans TW, Firth JD, Poole-Wilson PA. Tissue expression of endothelin-1 mRNA in endotoxaemia. Biochem Biophys Res Commun 1996; 218: 641-7.
  CrossrefPubMedGoogle Scholar
• 33 Ruetten H, Thiemermann C. Effect of selective blockade of endothelin ETB receptors on the liver dysfunction and injury caused by endotoxaemia in the rat. Br J Pharmacol 1996; 119: 479-86.
  CrossrefPubMedGoogle Scholar
• 34 Westberg G, Shultz PJ, Raij L. Exogenous nitric oxide prevents endotoxin-induced glomerular thrombosis in rats. Kidney Int 1994; 46: 711-6.
  CrossrefPubMedGoogle Scholar