Role of bradykinin B-2 and B-1 receptors in the local, remote, and systemic inflammatory responses that follow intestinal ischemia and reperfusion injury

Abstract

The administration of bradykinin may attenuate ischemia and reperfusion (I/R) injury by acting on B(2)Rs. Blockade of B2R 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 B2R antagonist (HOE 140) inhibited reperfusion-induced inflammatory tissue injury and delayed lethality. After I/R, there was an increase in the expression of B1R mRNA that was prevented by HOE 140. In mice that were deficient in B(1)Rs (B1R-/- 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 B1R-/- phenotype. Thus, B(2)Rs are a major driving force for B1R 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 B1R-/- 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. The Journal of Immunology, 2004, 172: 2542-2548.