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

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

Author Souza, Daniele G. Google Scholar
Pinho, Vanessa Google Scholar
Pesquero, Jorge L. Google Scholar
Lomez, Eliane S. Google Scholar
Poole, Steve Google Scholar
Juliano, Luiz Autor UNIFESP Google Scholar
Correa Junior, Ary Google Scholar
Castro, M Salete D Google Scholar
Teixeira, Mauro M. Google Scholar
Institution Universidade Federal de Minas Gerais (UFMG)
Universidade Federal de São Paulo (UNIFESP)
Natl Inst Biol Stand & Controls
Abstract 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.
Keywords ischemia and reperfusion
Language English
Date 2003-05-01
Published in British Journal of Pharmacology. London: Nature Publishing Group, v. 139, n. 1, p. 129-139, 2003.
ISSN 0007-1188 (Sherpa/Romeo, impact factor)
Publisher Nature Publishing Group
Extent 129-139
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000183125500015

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