Differential bradykinin B1 and B2 receptor regulation in cell death induced by hepatic ischemia-reperfusion injury

The biological and pharmacological effects of bradykinin (BK) are mediated by two receptors: the constitutive B2 receptor (B2R) and the inducible B1 receptor (B1R). BK plays a role in the hepatic microcirculation by inducing the portal hypertensive response (PHR) via B2R, whereas des-Arg9-BK (DABK), a B1R agonist, does not elicit the response. During ischemia-reperfusion injury, important changes occur in the microcirculation, and cell death by necrosis and apoptosis is involved in poor graft function. The aim of the present study was to analyze the role of B1R and B2R in liver cell death induced by ischemia-reperfusion injury. Livers from Wistar rats were submitted to ischemia (4°C) for 4 h or 24 h. After this period, the livers were reperfused ex vivo with Krebs-Henseleit solution (37°C). BK or DABK was injected in bolus during reperfusion in the presence or absence of HOE-140 (B2R) or des-arg9-[leu8]-BK (B1R), respectively. Liver viability was analyzed by glucose release and bile secretion. The PHR to kinins did not change. Cell death was higher in the DABK group and its antagonist significantly decreased cell death. Interestingly, B1R antagonist did not alter the number of necrotic cells, but it decreased the number of apoptotic cells. On the other hand, B2R antagonist decreased the number of necrotic cells and did not alter the number of apoptotic cells. Therefore, B1R may participate in apoptotic cell death signaling, and B2R may be involved in necrotic ce...
Source: Clinical Science - Category: Biomedical Science Authors: Source Type: research