Navegando por Palavras-chave "kinin B(1) receptor"

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    Increased susceptibility to endotoxic shock in transgenic rats with endothelial overexpression of kinin B(1) receptors
    (Springer, 2008-07-01) Merino, Vanessa F. [UNIFESP]; Todiras, Mihail; Campos, Luciana A.; Saul, Vera; Popova, Elena; Baltatu, Ovidiu C.; Pesquero, Joao B. [UNIFESP]; Bader, Michael; Max Delbruck Ctr Mol Med; Universidade Federal de São Paulo (UNIFESP)
    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.
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    The relevance of kinin B(1) receptor upregulation in a mouse model of colitis
    (Wiley-Blackwell, 2008-07-01) Hara, D. B.; Leite, D. F. P.; Fernandes, E. S.; Passos, G. F.; Guimaraes, Alessander de Oliveira [UNIFESP]; Pesquero, João Bosco [UNIFESP]; Campos, M. M.; Calixto, J. B.; Universidade Federal de Santa Catarina (UFSC); Universidade Federal de São Paulo (UNIFESP); Pontificia Univ Catolica Rio Grande do Sul
    Background and purpose: Kinins are implicated in many pathophysiological conditions, and recent evidence has suggested their involvement in colitis. This study assessed the role of the kinin B(1) receptors in a mouse model of colitis.Experimental approach: Colitis was induced in mice by 2,4,6-trinitrobenzene sulphonic acid (TNBS), and tissue damage and myeloperoxidase activity were assessed. B(1) receptor induction was analysed by organ bath studies, binding assay and reverse transcription PCR.Key results: TNBS-induced colitis was associated with tissue damage, neutrophil infiltration and time-dependent increase of colon B(1) receptor-mediated contraction, with the maximal response observed at 72 h. the upregulation of the B(1) receptor at this time point was also confirmed by means of binding studies. B(1) receptor mRNA levels were elevated as early as 6 h after colitis induction and remained high for up to 48 h. TNBS-evoked tissue damage and neutrophil influx were reduced by the selective B(1) receptor antagonist SSR240612, and in B(1) receptor knockout mice. in vivo treatment with inhibitors of protein synthesis, nuclear factor-kappa B activation, inducible nitric oxide synthase (iNOS) or tumour necrosis factor alpha (TNF alpha) significantly reduced B(1) receptor agonist-induced contraction. Similar results were observed in iNOS and TNF receptor 1-knockout mice.Conclusions and implications: These results provide convincing evidence on the role of B1 receptors in the pathogenesis of colitis. Therefore, the blockade of kinin B1 receptors might represent a new therapeutic option for treating inflammatory bowel diseases.