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| Item Type: | Article |
|---|---|
| Title: | Mice deficient for both kinin receptors are normotensive and protected from endotoxin- induced hypotension |
| Creators Name: | Cayla, C., Todiras, M., Iliescu, R., Saul, V.V., Gross, V., Pilz, B., Chai, G., Merino, V.F., Pesquero, J.B., Baltatu, O.C. and Bader, M. |
| 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. |
| Keywords: | Bradykinin, Blood pressure, Endotoxemia, Animals, Mice |
| Source: | FASEB Journal |
| ISSN: | 0892-6638 |
| Publisher: | Federation of American Societies for Experimental Biology |
| Volume: | 21 |
| Number: | 8 |
| Page Range: | 1689-1698 |
| Date: | June 2007 |
| Official Publication: | https://doi.org/10.1096/fj.06-7175com |
| PubMed: | View item in PubMed |
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