Effect of dopamine on inflammatory status in kidneys of brain-dead rats.
BACKGROUND
Brain death has been identified as an independent risk factor for chronic allograft dysfunction. In two independent retrospective clinical studies, we showed that dopamine treatment of brain-dead donors improves long-term kidney graft survival. The mechanisms underlying the protective effects of dopamine treatment in vivo have not been identified. To elucidate the mechanisms underlying the protective effect of dopamine on kidneys of brain-dead donors, we studied a model for brain death in rats.


METHODS
In F344 rats, brain death was induced by epidural inflation of a 3F Fogarty catheter. Apneic animals were mechanically ventilated, and clinically relevant dosages of dopamine (2, 6, 10, or 14 microg/kg/min) were given for 6 hr from the onset of brain death. Ventilated, non-brain-dead animals served as controls.


RESULTS
Dopamine significantly reduced renal monocyte infiltration and major histocompatibility class II and P-selectin expression in brain-dead animals. It also prevented further up-regulation of the inflammatory markers tumor necrosis factor-alpha and monocyte chemoattractant peptide-1. Concomitantly, the presence of inducible anti-oxidant heme oxygenase-1, known for its cytoprotective effects, was strongly increased by dopamine.


CONCLUSIONS
We identified several mechanisms underlying the protective effects of dopamine treatment on kidney grafts. The identification of these mechanisms may help to design more effective future strategies for treatment of cadaveric kidney donors.
Schaub
Meike
M
Fifth Medical Clinic, University Hospital Mannheim, Mannheim, Germany. mschaub@rumms.uni-mannheim.de
Ploetz
Christian J
CJ
Gerbaulet
Daniel
D
Fang
Liu
L
Kranich
Pia
P
Stadlbauer
Thomas H W
TH
Goettman
Uwe
U
Yard
Benito A
BA
Braun
Claude
C
Schnuelle
Peter
P
van der Woude
Fokko J
FJ
D000818:Animals; D001794:Blood Pressure; D015153:Blotting, Western; D001926:Brain Death; D004298:Dopamine / Q000494:pharmacology*; D015870:Gene Expression / Q000276:immunology; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D051547:Heme Oxygenase-1; D007668:Kidney / Q000276:immunology; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D009393:Nephritis / Q000188:drug therapy* / Q000276:immunology; D018384:Oxidative Stress / Q000187:drug effects / Q000276:immunology; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014019:Tissue Donors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D014409:Tumor Necrosis Factor-alpha; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D004298:Dopamine