Tacrolimus in acute renal failure: does L-arginine-infusion prevent changes in renal hemodynamics?
Nephrotoxicity is one of the main side effects of calcineurin-inhibitors. The influence of tacrolimus on the renal vasculature has not been well described. We have therefore examined the effects of tacrolimus on renal functional parameters as well as the contribution of the NO-system in a model of ischemic acute renal failure (ARF). Induction of ARF was achieved by clamping both renal arteries of female Sprague-Dawley rats. During the experiment, RBF, GFR, MAP, RVR and FENa were determined during infusion of vehicle, TAC, TAC and the NOS-activator L-arginine, and TAC and NOS-inhibition due to L-NMMA. TAC induced a significant rise in RVR with further decrease of RBF and GFR. Simultaneous L-arginine-infusion could reverse these effects during the infusion without complete restoration to preischemic levels. NOS-inhibition increased MAP and RBF without any effect on GFR. FENa did not differ significantly between the groups. Tacrolimus in the situation of ischemic acute renal failure causes vasoconstriction of pre- and postglomerular vessels with a further deterioration of renal function. L-arginine abolishes the functional deterioration, most likely due to increased NO-liberation.
Lopau
K
K
Department of Medicine, Division of Nephrology, University Hospital Wuerzburg, Josef-Schneider-Strasse 2, 97080 Wuerzburg, Germany. k.lopau@medizin.uni-wuerzburg.de
Kleinert
D
D
Erler
J
J
Schramm
L
L
Heidbreder
E
E
Wanner
C
C
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000517:prevention & control*; D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D065095:Calcineurin Inhibitors; D003250:Constriction; D004231:Diuresis / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000633:toxicity*; D007511:Ischemia / Q000209:etiology / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply*; D007678:Kidney Glomerulus / Q000098:blood supply / Q000187:drug effects; D009569:Nitric Oxide / Q000096:biosynthesis; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D012077:Renal Artery; D012079:Renal Circulation / Q000187:drug effects*; D016559:Tacrolimus / Q000494:pharmacology / Q000633:toxicity*; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D065095:Calcineurin Inhibitors; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D020030:Nitric Oxide Donors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D016559:Tacrolimus