Increased susceptibility to endotoxic shock in transgenic rats with endothelial overexpression of kinin B(1) 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.
Merino
Vanessa F
VF
Max Delbrück Center for Molecular Medicine, Robert-Rössle-Str. 10, Berlin-Buch, Berlin, 13125, Germany.
Todiras
Mihail
M
Campos
Luciana A
LA
Saul
Vera
V
Popova
Elena
E
Baltatu
Ovidiu C
OC
Pesquero
João B
JB
Bader
Michael
M
D000818:Animals; D030801:Animals, Genetically Modified; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002199:Capillary Permeability; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051381:Rats; D043783:Receptor, Bradykinin B1 / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D012772:Shock, Septic / Q000378:metabolism* / Q000503:physiopathology*; D013997:Time Factors
D008070:Lipopolysaccharides; D043783:Receptor, Bradykinin B1