gms | German Medical Science

27. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

Deutsche Liga zur Bekämpfung des hohen Blutdrucks – Deutsche Hypertonie Gesellschaft e. V.

26. bis 29.11.2003, Bonn

Differential mRNA Expression of Kinin Receptors in HPA Axis In LPS-Induced Inflammation

Expression der Kinin B1 und B2-Rezeptoren in der HPA-Achse nach LPS-induzierter Inflammation

Meeting Abstract (Hypertonie 2003)

  • presenting/speaker F. Rimmele - Inst. Exp. & Klin. Pharmakol. Toxikol. (Lübeck, D)
  • F. Qadri - Inst. Exp. & Klin. Pharmakol. Toxikol. (Lübeck, D)
  • W. Häuser - Inst. Exp. & Klin. Pharmakol. Toxikol. (Lübeck, D)
  • O. Jöhren - Inst. Exp. & Klin. Pharmakol. Toxikol. (Lübeck, D)
  • A. Dendorfer - Inst. Exp. & Klin. Pharmakol. Toxikol. (Lübeck, D)
  • P. Dominiak - Inst. Exp. & Klin. Pharmakol. Toxikol. (Lübeck, D)

Hypertonie 2003. 27. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Bonn, 26.-29.11.2003. Düsseldorf, Köln: German Medical Science; 2004. Doc03hochP86

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/hoch2003/03hoch186.shtml

Published: November 11, 2004

© 2004 Rimmele et al.
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Outline

Text

Lipopolysaccharide (LPS) induces several central effects such as fever, inhibition of water and food intake, anxiety and depressive-like episodes. It has been postulated that most central effects induced by LPS are mediated through cytokine and nitric oxide. Bradykinin (BK) and its active metabolite des-Arg9-BK are pro-inflammatory mediators. They act through the activation of B2 and B1 receptors, respectively. These neuromodulatory peptides influence the central regulation of blood pressure, pain and core temperature. Most of these physiological functions are mediated through B2 receptors present constitutively. The B1 receptors can be induced by LPS and cytokines. Therefore, we measured in male SD-rats the mRNA levels of kinin B1 and B2 receptors in the HPA axis 1, 3 and 6 h after a single i.p. injection of LPS and compared with control rats.

There was a significant and time-dependent increase in B1 mRNA levels in the hypothalamus, pituitary and adrenals of LPS-treated rats. The highest mRNA levels were found at 6 h following LPS. B2 mRNA levels were increased in the pituitary and adrenals, and no change was found in hypothalamus. We also localize the neurons within the brain which were activated following LPS i.p. by immunostaining of c-Fos expression, a transcriptional factor expressed immediately following neuronal activation. Pretreatment of rats with Lys-(des Arg9, Leu8)-BK, a specific B1 receptor antagonist, given intracerebroventricularly (200 pmol/2 µl) completely abolished the LPS-induced c-Fos expression in the hypothalamic PVN and SON. Whereas, pretreatment of rats with Hoe 140, a specific B2 receptor antagonist, did not completely abolished the LPS-induced c-Fos expression.

Our present molecular and anatomical data provide evidence that the effects induced by LPS given i.p. are mediated through the enhanced mRNA expression of kinin B1 and B2 receptors in the HPA axis which may reflect a functional relationship.