Regulators of angiogenesis in renal ischemia/reperfusion injury in normotensive and hypertensive rats: effect of tacrolimus

Transplant Proc. 2005 Jan-Feb;37(1):352-4. doi: 10.1016/j.transproceed.2004.12.154.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Blood Pressure
  • Disease Models, Animal
  • Fibroblast Growth Factor 2 / genetics
  • Hypertension / physiopathology*
  • Kidney Transplantation / immunology
  • Kidney Transplantation / physiology*
  • Kidney*
  • Neovascularization, Pathologic / prevention & control*
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / pathology*
  • Tacrolimus / therapeutic use*

Substances

  • Fibroblast Growth Factor 2
  • Tacrolimus