Treatment of organ donors with
catecholamines reduces acute rejection episodes and improves long-term graft survival after
renal transplantation. The aim of this study was to investigate the effect of
catecholamine pre-treatment on
ischemia/reperfusion (I/R)- and cold preservation injury in rat kidneys. I/R-injury was induced by clamping the left kidney vessels for 60 min along with a contralateral
nephrectomy. Cold preservation injury was induced by storage of the kidneys for 24 h at +4 degrees Celsius in University of Wisconsin
solution, followed by
syngeneic transplantation. Rats were pre-treated with either
dopamine (DA),
dobutamine (DB), or
norepinephrine (2, 5, and 10 microg/kg/min, each group) intravenously via an osmotic minipump for 24 h before I/R- and cold preservation injury. Pre-treatment with DA (2 or 5 microg/kg/min) and DB (5 microg/kg/min) improved recovery of renal function after I/R-injury and dose dependently reduced mononuclear and major histocompatibility complex class II-positive cells infiltrating the kidney after I/R-injury. One day after I/R-injury, upregulation of
transforming growth factor (
TGF)-beta 1 and 2 and phosphorylation of p42/p44
mitogen-activated protein kinases was observed in kidneys of animals treated with DA or DB. DA (5 microg/kg/min) and DB (5 microg/kg/min) pre-treatment reduced endothelial cell damage after 24 h of cold preservation. Only DA pre-treatment improved renal function and reduced renal
inflammation after 24 h of cold preservation and
syngeneic transplantation. Our results demonstrate a protective effect of pre-treatment with
catecholamines on renal
inflammation and function after I/R- or cold preservation injury. This could help to explain the potent organoprotective effects of
catecholamine pre-treatment observed in human
kidney transplantation.