title: Pentoxifylline decreases cyclosporine-induced renal endothelin release and vasoconstriction.
abstract: 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.
authors.affiliation: Department of Surgery, Montreal Heart Institute, Quebec, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Carrier
authors.forename: L P
authors.initials: LP
authors.lastname: Perrault
authors.forename: F
authors.initials: F
authors.lastname: Tronc
authors.forename: D J
authors.initials: DJ
authors.lastname: Stewart
authors.forename: C L
authors.initials: CL
authors.lastname: Pelletier
mesh_terms: 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*
chemical_list: D016232:Endothelins; D016572:Cyclosporine; D010431:Pentoxifylline