Dopamine treatment in brain-dead rats mediates anti-inflammatory effects: the role of hemodynamic stabilization and D-receptor stimulation.
Brain death (BD) is associated with profound inflammation in end-organs. Dopamine (DA) treatment reduces this inflammatory response, but the underlying mechanisms remain thus far largely unknown. In this study, we investigated if the anti-inflammatory effect of DA was related to hemodynamic stabilization and by which receptors it was mediated. BD was induced in F344 donor rats. DA was given either before BD for 24 h or after BD induction during a definite time. Adrenergic or D-receptor blockers were administered to inhibit the receptor stimulation mediated by DA. Hemodynamic changes were recorded and kidneys were harvested after 6 h of BD. Mean arterial pressure was completely normalized by DA treatment. DA pretreatment before BD induction and treatment during BD both significantly inhibited the monocyte infiltration. The anti-inflammatory as well as its blood pressure stabilizing effect was abrogated by concomitant application of adrenergic receptor blockers. In contrast, concomitant application of D-receptor blockers only abrogated the anti-inflammatory effect, but did not affect blood pressure stabilization. In contrast, pergolide and adrenergic receptor blockers completely normalized the blood pressure, but did not affect renal inflammation. Hence, DA might reduce BD-induced monocyte infiltration possibly by hemodynamic stabilization, D-receptor activation, or a combination of both.
Hoeger
Simone
S
Department of Medicine V, University Medical Center Mannheim, University of Heidelberg, Germany, and Départment de Médecine, Interne et Néphrologie, Centre Hospitalier Kirchberg, Luxembourg. simone.hoeger@urz.uni-heidelberg.de
Gottmann
Uwe
U
Liu
Zhenzi
Z
Schnuelle
Peter
P
Birck
Rainer
R
Braun
Claude
C
van der Woude
Fokko J
FJ
Yard
Benito A
BA
D018674:Adrenergic Antagonists / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D001926:Brain Death / Q000503:physiopathology*; D015815:Cell Adhesion Molecules / Q000097:blood; D002469:Cell Separation; D004298:Dopamine / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000235:genetics; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D009393:Nephritis / Q000517:prevention & control*; D010479:Pergolide / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D011954:Receptors, Dopamine / Q000187:drug effects*
D018674:Adrenergic Antagonists; D000893:Anti-Inflammatory Agents; D015815:Cell Adhesion Molecules; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D010479:Pergolide; D051547:Heme Oxygenase-1; D004298:Dopamine