Pentoxifylline decreases cyclosporine-induced renal endothelin release and vasoconstriction.
Cyclosporine (CSA) causes an acute vasoconstriction of renal artery and a significant increase in renal endothelin release. Pentoxifylline, a vasodilator, has been suggested to prevent CSA toxicity. To study the effect of pentoxifylline treatment on CSA-related vasoconstriction and endothelin release, a model of renal autoperfusion in the dog was used. Oral pentoxifylline at the dose of 400 mg three times daily for 3 days was given to 15 dogs. Pure powder CSA (10 mg) was injected into the isolated renal artery perfused at constant flow; changes in perfusion pressure reflected variations in vascular resistance. In the pentoxifylline-treated group (15 dogs), the infusion of CSA caused an average increase of 27 +/- 8 mm Hg in renal perfusion pressure, compared with 60 +/- 10 mm Hg in a control group of 8 untreated animals (p < or = 0.05). Plasma concentration of endothelin in the renal vein increased from an average of 1.2 +/- 0.2 pg/mL before to 2.4 +/- 0.5 pg/mL after CSA administration (p < or = 0.05) in the control group, whereas it did not change significantly in the pentoxifylline-treated group. Thus, oral pretreatment with pentoxifylline significantly decreased the renal vasoconstriction and endothelin release due to CSA administration.
Carrier
M
M
Department of Surgery, Montreal Heart Institute, Quebec, Canada.
Perrault
L P
LP
Tronc
F
F
Stewart
D J
DJ
Pelletier
C L
CL
D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology*; D004285:Dogs; D016232:Endothelins / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D010431:Pentoxifylline / Q000494:pharmacology*; D012077:Renal Artery / Q000187:drug effects* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects*
D016232:Endothelins; D016572:Cyclosporine; D010431:Pentoxifylline