Bradykinin B1 and B2 receptors both have protective roles in renal ischemia/reperfusion injury.
To explore the role of the kallikrein-kinin system in relation to ischemia/reperfusion injury in the kidney, we generated mice lacking both the bradykinin B1 and B2 receptor genes (B1RB2R-null, Bdkrb1-/-/Bdkrb2-/-) by deleting the genomic region encoding the two receptors. In 4-month-old mice, blood pressures were not significantly different among B1RB2R-null, B2R-null (Bdkrb2-/-), and WT mice. After 30 min of bilateral renal artery occlusion and 24 h of reperfusion, mortality rates, renal histological and functional changes, 8-hydroxy-2'-deoxyguanosine levels in total DNA, mtDNA deletions, and the number of TUNEL-positive cells in the kidneys increased progressively in the following order (from lowest to highest): WT, B2R-null, and B1RB2R-null mice. Increases in mRNA levels of TGF-beta1, connective tissue growth factor, and endothelin-1 after ischemia/reperfusion injury were also exaggerated in the same order (from lowest to highest): WT, B2R-null, and B1RB2R-null. Thus, both the B1 and B2 bradykinin receptors play an important role in reducing DNA damage, apoptosis, morphological and functional kidney changes, and mortality during renal ischemia/reperfusion injury.
Kakoki
Masao
M
Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599-7525, USA. mkakoki@med.unc.edu
McGarrah
Robert W
RW
Kim
Hyung-Suk
HS
Smithies
Oliver
O
D000818:Animals; D007674:Kidney Diseases / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D012333:RNA, Messenger / Q000235:genetics; D043783:Receptor, Bradykinin B1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D043782:Receptor, Bradykinin B2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control*
D009566:Nitrates; D009573:Nitrites; D012333:RNA, Messenger; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2