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Title: Mice deficient for both kinin receptors are normotensive and protected from endotoxin-induced hypotension
Authors: Cayla, Cecile
Todiras, Mihail
Iliescu, Radu
Saul, Vera V.
Gross, Volkmar
Pilz, Bernhard
Chai, Guixuan
Merino, Vanessa F.
Pesquero, Joao B. [UNIFESP]
Baltatu, Ovidiu C.
Bader, Michael
Max Delbruck Ctr Mol Med
Helios Klinikum Berlin
Universidade Federal de São Paulo (UNIFESP)
Keywords: bradykinin
blood pressure
Issue Date: 1-Jun-2007
Publisher: Federation Amer Soc Exp Biol
Citation: Faseb Journal. Bethesda: Federation Amer Soc Exp Biol, v. 21, n. 8, p. 1689-1698, 2007.
Abstract: Kinins play a central role in the modulation of cardiovascular function and in the pathophysiology of inflammation. These peptides mediate their effects by binding to two specific G-protein coupled receptors named B1 and B2. To evaluate the full functional relevance of the kallikrein- kinin system, we generated mice lacking both kinin receptors (B1B2-/-). Because of the close chromosomal position of both kinin receptor genes, B1B2-/- mice could not be obtained by simple breeding of the single knockout lines. Therefore, we inactivated the B1 receptor gene by homologous recombination in embryonic stem cells derived from B2-deficient animals. the B1B2-/- mice exhibited undetectable levels of mRNAs for both receptors and a lack of response to bradykinin (B2 agonist) and des-Arg(9)-bradykinin (B1 agonist), as attested by contractility studies with isolated smooth muscle tissues. B1B2-/- mice are healthy and fertile, and no sign of cardiac abnormality was detected. They are normotensive but exhibit a lower heart rate than controls. Furthermore, kinin receptor deficiency affects the pathogenesis of endotoxin- induced hypotension. While blood pressure decreased markedly in wild-type mice and B2-/- and moderately in B1-/- mice after bacterial lipopolysaccharide ( LPS) injection, blood pressure remained unchanged in B1B2-/- mice. These results clearly demonstrate a pivotal role of kinins and their receptors in hypotension induced by endotoxemia in mice.-Cayla, C., Todiras, M., Iliescu, R., Saul, V. V., Gross, V., Pilz, B., Chai, G., Merino, V. F., Pesquero, J. B., Baltatu, O. C., Bader, M. Mice deficient for both kinin receptors are normotensive and protected from endotoxin-induced hypotension.
ISSN: 0892-6638
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