| Dokumentenart: | Artikel | ||||
|---|---|---|---|---|---|
| Titel eines Journals oder einer Zeitschrift: | Critical Care Medicine | ||||
| Verlag: | LIPPINCOTT WILLIAMS & WILKINS | ||||
| Ort der Veröffentlichung: | PHILADELPHIA | ||||
| Band: | 36 | ||||
| Nummer des Zeitschriftenheftes oder des Kapitels: | 8 | ||||
| Seitenbereich: | S. 2363-2372 | ||||
| Datum: | 2008 | ||||
| Institutionen: | Medizin > Lehrstuhl für Anästhesiologie Biologie und Vorklinische Medizin > Institut für Physiologie | ||||
| Identifikationsnummer: |
| ||||
| Stichwörter / Keywords: | NITRIC-OXIDE SYNTHASE; IN-VIVO INHIBITION; SEPTIC SHOCK; PYRROLIDINE DITHIOCARBAMATE; ANGIOTENSIN-II; ARGININE-VASOPRESSIN; DOWN-REGULATION; CARDIOVASCULAR-SYSTEM; CONSCIOUS RATS; PROTECTS MICE; vasopressin V-1A-receptors; sepsis; NF-kappa B | ||||
| Dewey-Dezimal-Klassifikation: | 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin | ||||
| Status: | Veröffentlicht | ||||
| Begutachtet: | Ja, diese Version wurde begutachtet | ||||
| An der Universität Regensburg entstanden: | Ja | ||||
| Dokumenten-ID: | 67942 |
Web of ScienceZusammenfassung
Objective: Here we characterize the impact of nuclear factor-kappa B and cytokines on cecal ligation and puncture-induced circulatory failure and regulation of vasopressin V-1A-receptors during inflammation. Design: Prospective animal trial. Setting: Laboratory of the Department of Anesthesiology. Subjects: Male C57/BL6 mice. Interventions: The effects of cecal ligation and puncture on ...
Zusammenfassung
Objective: Here we characterize the impact of nuclear factor-kappa B and cytokines on cecal ligation and puncture-induced circulatory failure and regulation of vasopressin V-1A-receptors during inflammation. Design: Prospective animal trial. Setting: Laboratory of the Department of Anesthesiology. Subjects: Male C57/BL6 mice. Interventions: The effects of cecal ligation and puncture on hemodynamic parameters and V-1A-receptor expression were measured in cytokine knock-out mice, in mice with/without treatment with glucocorticoids or NF-kappa B-inhibitors, in mice pretreated with small interfering RNA silencing NF-kappa B and in mice treated with V, receptor agonists. Furthermore, the effects of cytokines on VIA-receptor expression were determined. Measurements and Main Results. Cecal ligation and puncture resulted in a hyperdynamic circulatory failure with diminished blood pressor dose response to V, receptor agonists and down-regulation of V-1A-receptors. Dexamethasone inhibited proinflammatory cytokine production and attenuated cecal ligation and puncture-induced cardiovascular failure in parallel with attenuated down-regulation of V-1A-receptor expression. Tumor necrosis factor-alpha, interleukin-1 beta, interferon-gamma or interleukin-6 dose-dependently decreased V-1A-receptor expression, whereas cecal ligation and puncture-induced down-regulation of V-1A-receptors was not affected in cytokine knock-out mice. In contrast, inhibition of NF-kappa B strongly reduced induction of cytokines, prevented septic circulatory failure and down-regulation of V-1A-receptor gene expression and improved survival of septic animals. Conclusions: Our data demonstrate that down-regulation of V-1A-receptor expression during sepsis may be due to proinflammatory cytokines. Our findings explain the failure of therapeutic strategies targeting single cytokines as well as the success of glucocorticoid therapy and define a critical role for NF-kappa B in the pathogenesis of septic shock.
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