Increased susceptibility to endotoxic shock in transgenic rats with endothelial overexpression of kinin B1 receptors

Vanessa F. Merino, Mihail Todiras, Luciana A. Campos, Vera Saul, Elena Popova, Ovidiu C. Baltatu, João B. Pesquero, Michael Bader

Research output: Contribution to journalArticle

Abstract

Two kinin receptors have been described, the inducible B1 and the constitutive B2. B1 receptors are important in cardiovascular homeostasis and inflammation. To further clarify their vascular function, we have generated transgenic rats (TGR(Tie2B1)) overexpressing the B1 receptor exclusively in the endothelium. Endothelial cell-specific expression was confirmed by B1-agonist- induced relaxation of isolated aorta, which was abolished by endothelial denudation of the vessel. This vasodilatation was mediated by nitric oxide (NO) and K+ channels. TGR(Tie2B1) rats were normotensive but, in contrast to controls, reacted with a marked fall in blood pressure and increased vascular permeability after intravenous injection of a B1 agonist. After lipopolysaccharide treatment, they present a more pronounced hypotensive response and marked bradycardia associated with increased mortality when compared to non-transgenic control animals. Thus, the transgenic rats overexpressing kinin B1 receptors exclusively in the endothelium generated in this study support an important role of this receptor in the vasculature during the pathogenesis of endotoxic shock.

Original languageEnglish (US)
Pages (from-to)791-798
Number of pages8
JournalJournal of Molecular Medicine
Volume86
Issue number7
DOIs
StatePublished - Jul 1 2008
Externally publishedYes

Keywords

  • Endothelium
  • Endotoxic shock
  • Hypotension
  • Kinin B receptor
  • Transgenic

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Genetics(clinical)

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