Role of bradykinin B2 and B1 receptors in the local, remote, and systemic inflammatory responses that follow intestinal ischemia and reperfusion injury.
The administration of bradykinin may attenuate ischemia and reperfusion (I/R) injury by acting on B(2)Rs. Blockade of B(2)R has also been shown to ameliorate lesions associated with I/R injury. In an attempt to explain these contradictory results, the objective of the present work was to investigate the role of and interaction between B(1) and B(2) receptors in a model of intestinal I/R injury in mice. The bradykinin B(2)R antagonist (HOE 140) inhibited reperfusion-induced inflammatory tissue injury and delayed lethality. After I/R, there was an increase in the expression of B(1)R mRNA that was prevented by HOE 140. In mice that were deficient in B(1)Rs (B(1)R(-/-) mice), inflammatory tissue injury was abrogated, and lethality was delayed and partially prevented. Pretreatment with HOE 140 reversed the protective anti-inflammatory and antilethality effects provided by the B(1)R(-/-) phenotype. Thus, B(2)Rs are a major driving force for B(1)R activation and consequent induction of inflammatory injury and lethality. In contrast, activation of B(2)Rs may prevent exacerbated tissue injury and lethality, an effect unmasked in B(1)R(-/-) mice and likely dependent on the vasodilatory actions of B(2)Rs. Blockade of B(1)Rs could be a more effective strategy than B(2) or B(1)/B(2) receptor blockade for the treatment of the inflammatory injuries that follow I/R.
Souza
Danielle G
DG
Departamentos de. Bioquímica e Imunologia, e Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Brazil.
Lomez
Eliane S L
ES
Pinho
Vanessa
V
Pesquero
João Bosco
JB
Bader
Michael
M
Pesquero
Jorge Luís
JL
Teixeira
Mauro M
MM
D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D065169:Bradykinin B1 Receptor Antagonists; D065094:Bradykinin B2 Receptor Antagonists; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D016207:Cytokines / Q000032:analysis / Q000097:blood; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D020382:Interleukin-18 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000098:blood supply* / Q000276:immunology / Q000473:pathology; D008168:Lung / Q000737:chemistry / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000096:biosynthesis; D020239:Receptor Cross-Talk / Q000502:physiology; D043783:Receptor, Bradykinin B1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D043782:Receptor, Bradykinin B2 / Q000502:physiology*; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology*
D065169:Bradykinin B1 Receptor Antagonists; D065094:Bradykinin B2 Receptor Antagonists; D018932:Chemokine CCL2; D016207:Cytokines; D018836:Inflammation Mediators; D007375:Interleukin-1; D020382:Interleukin-18; D012333:RNA, Messenger; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; C065679:icatibant; D001920:Bradykinin