title: Regulators of angiogenesis in renal ischemia/reperfusion injury in normotensive and hypertensive rats: effect of tacrolimus.
abstract: The aim of this study was to evaluate the role of proangiogenic growth factors in an experimental model of ischemia/reperfusion injury (I/R) in both normotensive and hypertensive rats. Renal ischemic injury was induced in transgenic rats rendered hypertensive due to renin overproduction [TGR (mREN-2)-27] and in normotensive Hannover Sprague-Dawley rats (HanSD). Animals were treated for 12 weeks with either tacrolimus (TAC, 0.1 mg/kg per day, intramuscularly [IM]) or placebo. After 12 weeks, kidneys were harvested for morphologic, immunohistochemical, and RT-PCR analysis. Both normotensive and hypertensive untreated rats developed significantly greater proteinuria and glomerulosclerosis compared with TAC-treated rats. Immunohistologically, TGR showed higher basic fibroblast growth factor (bFGF) protein expression compared with normotensive HanSD. TAC-treated rats had higher bFGF protein expression than untreated rats. Vascular endothelial growth factor (VEGF) protein expression in glomeruli was more increased in TGR after I/R than in sham-operated animals. TAC-treated TGR hosts developed higher VEGF mRNA expression compared with both untreated and sham groups; however, there were no differences between treated and untreated normotensive HanSD animals. bFGF is involved in the fibrogenesis induced by hypertension and I/R injury. The nature of the increase in proangiogeneic growth factor expression among tacrolimus-treated animals remains to be elucidated.
authors.affiliation: Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors.forename: J
authors.initials: J
authors.lastname: Rajnoch
authors.forename: A
authors.initials: A
authors.lastname: Lodererova
authors.forename: A
authors.initials: A
authors.lastname: Szabo
authors.forename: E
authors.initials: E
authors.lastname: Honsova
authors.forename: A
authors.initials: A
authors.lastname: Vannay
authors.forename: S
authors.initials: S
authors.lastname: Bloudickova
authors.forename: I
authors.initials: I
authors.lastname: Matl
authors.forename: O
authors.initials: O
authors.lastname: Viklicky
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001794:Blood Pressure; D004195:Disease Models, Animal; D016222:Fibroblast Growth Factor 2 / Q000235:genetics; D006973:Hypertension / Q000503:physiopathology*; D007668:Kidney; D016030:Kidney Transplantation / Q000276:immunology / Q000502:physiology*; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology*; D016559:Tacrolimus / Q000627:therapeutic use*
chemical_list: D016222:Fibroblast Growth Factor 2; D016559:Tacrolimus