Regulators of angiogenesis in renal ischemia/reperfusion injury in normotensive and hypertensive rats: effect of tacrolimus.
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.
Rajnoch
J
J
Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Lodererova
A
A
Szabo
A
A
Honsova
E
E
Vannay
A
A
Bloudickova
S
S
Matl
I
I
Viklicky
O
O
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*
D016222:Fibroblast Growth Factor 2; D016559:Tacrolimus