Role of the bradykinin B-2 receptor for the local and systemic inflammatory response that follows severe reperfusion injury

• Autor(a) principal: Souza, Daniele G.
• Data de Publicação: 2003
• Outros Autores: Pinho, Vanessa, Pesquero, Jorge L., Lomez, Eliane S., Poole, Steve, Juliano, Luiz [UNIFESP], Correa Junior, Ary, Castro, M Salete D, Teixeira, Mauro M.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNIFESP
• Texto Completo: http://dx.doi.org/10.1038/sj.bjp.0705200; http://repositorio.unifesp.br/handle/11600/27215
• topic: ischemia and reperfusion; cytokines; TNF-alpha; bradykinin; neutrophils; shock

1 Bradykinin (BK) appears to play an important role in the development and maintenance of inflammation. Here, we assessed the role of the BK B-2 receptor for the injuries that occur after ischemia and reperfusion (I/R) of the territory irrigated by the superior mesenteric artery.2 Tissue (lung and duodenum) kallikrein activity increased after ischemia with greater enhancement after reperfusion. A selective inhibitor of tissue kallikrein, Phenylacetyl-Phe-Ser-Arg-N-(2,3-dinitrophenyl)-ethylenediamine (TKI, 0.001 - 10 mg ml(-1)), inhibited kallikrein activity in a concentration-dependent manner in vitro. in vivo, pretreatment with TKI (30 mg kg(-1)) prevented the extravasation of plasma and the recruitment of neutrophils.3 Similarly, the bradykinin B-2 receptor antagonists, HOE 140 (0.01-1.0 mg kg(-1)) or FR173657 (10.0 mg kg(-1)), inhibited reperfusion-induced increases in vascular permeability and the recruitment of neutrophils in the intestine and lungs.4 in a model of more severe I/R injury, HOE 140 (1.0mg kg(-1)) inhibited the increase in vascular permeability, neutrophil recruitment, haemorrhage and tissue pathology. Furthermore, HOE 140 significantly inhibited the elevations of TNF-alpha in tissue and serum and partially prevented lethality. This was associated with an increase in the concentrations of IL-10 in tissue and serum.5 Thus, our results demonstrate that, following intestinal I/R injury, there is an increase in tissue kallikrein activity and activation of BK B-2 receptors. B-2 receptor activation is essential for the development of inflammatory tissue injury and lethality. These results contrast with those of others showing that BK mostly exerts a protective role during I/R injury.