Bradykinin B1 and B2 receptors both have protective roles in renal
ischemia/reperfusion injury
Authors Kakoki M, McGarrah RW, Kim H-S, Smithies O
Submitted By Oliver Smithies on 2/10/2009
Status Published
Journal Proceedings of the National Academy of Sciences of the United States of America
Year 2007
Date Published 5/1/2007
Volume : Pages 104 : 7576 - 7581
PubMed Reference 17452647
Abstract 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.

Investigators with authorship
Oliver SmithiesUniversity of North Carolina


Bdkrb2bradykinin receptor, beta 2
Tgfb1transforming growth factor, beta 1