Bradykinin [corrected] B1 receptor antagonism is beneficial in renal ischemia-reperfusion injury.
Previously we have demonstrated that bradykinin B1 receptor deficient mice (B1KO) were protected against renal ischemia and reperfusion injury (IRI). Here, we aimed to analyze the effect of B1 antagonism on renal IRI and to study whether B1R knockout or antagonism could modulate the renal expression of pro and anti-inflammatory molecules. To this end, mice were subjected to 45 minutes ischemia and reperfused at 4, 24, 48 and 120 hours. Wild-type mice were treated intra-peritoneally with antagonists of either B1 (R-954, 200 microg/kg) or B2 receptor (HOE140, 200 microg/kg) 30 minutes prior to ischemia. Blood samples were collected to ascertain serum creatinine level, and kidneys were harvested for gene transcript analyses by real-time PCR. Herein, B1R antagonism (R-954) was able to decrease serum creatinine levels, whereas B2R antagonism had no effect. The protection seen under B1R deletion or antagonism was associated with an increased expression of GATA-3, IL-4 and IL-10 and a decreased T-bet and IL-1beta transcription. Moreover, treatment with R-954 resulted in lower MCP-1, and higher HO-1 expression. Our results demonstrated that bradykinin B1R antagonism is beneficial in renal IRI.
Wang
Pamella H M
PH
Laboratório de Imunologia Clínica e Experimental, Division of Nephrology, Universidade Federal de São Paulo, São Paulo, Brazil.
Campanholle
Gabriela
G
Cenedeze
Marcos A
MA
Feitoza
Carla Q
CQ
Gonçalves
Giselle M
GM
Landgraf
Richardt G
RG
Jancar
Sonia
S
Pesquero
João B
JB
Pacheco-Silva
Alvaro
A
Câmara
Niels O S
NO
D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000627:therapeutic use; D065169:Bradykinin B1 Receptor Antagonists; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death; D017931:DNA Primers; D050990:GATA3 Transcription Factor / Q000627:therapeutic use; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006801:Humans; D016753:Interleukin-10 / Q000627:therapeutic use; D015847:Interleukin-4 / Q000627:therapeutic use; D007668:Kidney / Q000502:physiology / Q000503:physiopathology; D007674:Kidney Diseases / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D043783:Receptor, Bradykinin B1 / Q000172:deficiency / Q000235:genetics; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D017741:Survivors
C476306:Ac-Orn-(Oic2, alpha-MePhe5, D-betaNal7, Ile8)desArg9-bradykinin; D065169:Bradykinin B1 Receptor Antagonists; D017931:DNA Primers; D050990:GATA3 Transcription Factor; D043783:Receptor, Bradykinin B1; D016753:Interleukin-10; D015847:Interleukin-4; D053148:Caspase 3; D001920:Bradykinin