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

Two kinin receptors have been described, the inducible B 1 and the constitutive B 2 . B 1 receptors are important in cardiovascular homeostasis and inflammation. To further clarify their vascular function, we have generated transgenic rats (TGR(Tie2B 1 )) overexpressing the B 1 receptor exclusively in the endothelium. Endothelial cell-specific expression was confirmed by B 1 -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(Tie2B 1 ) 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 B 1 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 B 1 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.