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 language | English (US) |
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Pages (from-to) | 791-798 |
Number of pages | 8 |
Journal | Journal of Molecular Medicine |
Volume | 86 |
Issue number | 7 |
DOIs | |
State | Published - Jul 2008 |
Externally published | Yes |
Keywords
- Endothelium
- Endotoxic shock
- Hypotension
- Kinin B receptor
- Transgenic
ASJC Scopus subject areas
- Molecular Medicine
- Drug Discovery
- Genetics(clinical)