title: N-octanoyl dopamine treatment exerts renoprotective properties in acute kidney injury but not in renal allograft recipients.
abstract: N-octanoyl dopamine (NOD) treatment improves renal function when applied to brain dead donors and in the setting of warm ischaemia-induced acute kidney injury (AKI). Because it also activates transient receptor potential vanilloid type 1 (TRPV1) channels, we first assessed if NOD conveys its renoprotective properties in warm ischaemia-induced AKI via TRPV1 and secondly, if renal transplant recipients also benefit from NOD treatment.
  
  
  
  We induced warm renal ischaemia in Lewis, wild-type (WT) and TRPV1(-/-) Sprague-Dawley (sd) rats by clamping the left renal artery for 45 min. Transplantations were performed in allogeneic and syngeneic donor-recipient combinations (Fisher to Lewis and Lewis to Lewis) with a cold ischaemia time of 20 h. Treatment was instituted directly after restoration of organ perfusion. Renal function, histology and perfusion were assessed by serum creatinine, microscopy and magnetic resonance imaging (MRI) using arterial spin labelling (ASL).
  
  
  
  NOD treatment significantly improved renal function in Lewis rats after warm ischaemia-induced AKI. It was, however, not effective after prolonged cold ischaemia. The renoprotective properties of NOD were only observed in Lewis or WT, but not in TRPV1(-/-) sd rats. Renal inflammation was significantly abrogated by NOD. MRI-ASL showed a significantly lower cortical perfusion in ischaemic when compared with non-ischaemic kidneys. No overall differences were observed in renal perfusion between NOD- and NaCl-treated rats.
  
  
  
  NOD treatment reduces renal injury in warm ischaemia, but is not effective in renal transplant in our experimental animal models. The salutary effect of NOD appears to be TPRV1-dependent, not involving large changes in renal perfusion.
authors.affiliation: Vth Department of Medicine, University Hospital Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Klotz
authors.affiliation: Vth Department of Medicine, University Hospital Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany Institute for Molecular and Cellular Biology, Mannheim University of Applied Sciences, Mannheim, Germany.
authors.forename: Prama
authors.initials: P
authors.lastname: Pallavi
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, University Hospital Mannheim, Mannheim, Germany.
authors.forename: Charalambos
authors.initials: C
authors.lastname: Tsagogiorgas
authors.affiliation: Computer Assisted Clinical Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Zimmer
authors.affiliation: Computer Assisted Clinical Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Frank G
authors.initials: FG
authors.lastname: Zöllner
authors.affiliation: Division of Neurophysiology, Centre of Biomedicine and Medical Technology Mannheim (CBTM), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Uta
authors.initials: U
authors.lastname: Binzen
authors.affiliation: Division of Neurophysiology, Centre of Biomedicine and Medical Technology Mannheim (CBTM), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Greffrath
authors.affiliation: Division of Neurophysiology, Centre of Biomedicine and Medical Technology Mannheim (CBTM), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Rolf-Detlef
authors.initials: RD
authors.lastname: Treede
authors.affiliation: Bayer Healthcare Pharma AG, Berlin, Germany.
authors.forename: Jakob
authors.initials: J
authors.lastname: Walter
authors.affiliation: Department of Pathology and Medical Biology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
authors.forename: Martin C
authors.initials: MC
authors.lastname: Harmsen
authors.affiliation: Vth Department of Medicine, University Hospital Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Bernhard K
authors.initials: BK
authors.lastname: Krämer
authors.affiliation: Institute for Molecular and Cellular Biology, Mannheim University of Applied Sciences, Mannheim, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Hafner
authors.affiliation: Vth Department of Medicine, University Hospital Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Benito A
authors.initials: BA
authors.lastname: Yard
authors.affiliation: Vth Department of Medicine, University Hospital Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Hoeger
mesh_terms: D058186:Acute Kidney Injury / Q000188:drug therapy*; D000818:Animals; D004298:Dopamine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology* / Q000601:surgery; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D014019:Tissue Donors; D014184:Transplantation, Homologous; D052096:Warm Ischemia
chemical_list: C554838:N-octanoyldopamine; D004298:Dopamine
keywords: AKI; TRPV1; ischaemia; rat; renal transplantation