title: Calcitriol ameliorates capillary deficit and fibrosis of the heart in subtotally nephrectomized rats.
abstract: BACKGROUND
  Remodelling of the heart, characterized by hypertrophy, fibrosis and capillary/myocyte mismatch, is observed in patients with chronic renal failure. Low vitamin D levels have been associated with increased cardiovascular risk. In the present experimental study, we studied the effects of non-hypercalcaemic doses of calcitriol on microvascular disease and interstitial fibrosis of the heart.
  
  
  METHODS
  Three-month-old male Sprague-Dawley rats were randomized to subtotal nephrectomy (SNX) or sham operation and received calcitriol (6 ng/kg) or vehicle starting immediately thereafter. Blood pressure was measured by tail pletysmography. Albuminuria was measured by rat-specific ELISA. Capillary length density, volume density of interstitial tissue, immunohistochemistry and western blots (vitamin D receptor, collagen I, III, TGF-beta(1), MAP kinases and nitrotyrosine) were assessed after 12 weeks of treatment.
  
  
  RESULTS
  After SNX blood pressure, albuminuria and heart weight were elevated, capillary length density reduced and interstitial fibrosis increased. Treatment with calcitriol reduced albuminuria and prevented reduction of capillary density and expansion of interstitium without affecting significant blood pressure and heart weight after perfusion fixation. Calcitriol left high VEGF unchanged, but upregulated VEGF receptor 2 (presumably reversing VEGF resistance). Calcitriol reduced expression of profibrotic TGF-beta(1) and the accumulation of collagens I and III.
  
  
  CONCLUSIONS
  Non-hypercalcaemic doses of calcitriol ameliorated, directly or indirectly, cardiac remodelling in sub- totally nephrectomized rats.
authors.affiliation: Department of Pathology, Insitute of Pathology, University of Heidelberg, Heidelberg, Germany. nad_ko@gmx.de
authors.forename: Nadezda
authors.initials: N
authors.lastname: Koleganova
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Piecha
authors.forename: Eberhard
authors.initials: E
authors.lastname: Ritz
authors.forename: Marie-Luise
authors.initials: ML
authors.lastname: Gross
mesh_terms: D000818:Animals; D002117:Calcitriol / Q000627:therapeutic use*; D002196:Capillaries / Q000473:pathology; D004195:Disease Models, Animal; D005355:Fibrosis / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D006331:Heart Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D007676:Kidney Failure, Chronic / Q000150:complications*; D008297:Male; D009392:Nephrectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D020257:Ventricular Remodeling / Q000187:drug effects* / Q000502:physiology; D014815:Vitamins / Q000627:therapeutic use*
chemical_list: D014815:Vitamins; D002117:Calcitriol