NDT Advance Access originally published online on October 1, 2008
Nephrology Dialysis Transplantation 2009 24(3):778-787; doi:10.1093/ndt/gfn549
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Calcitriol ameliorates capillary deficit and fibrosis of the heart in subtotally nephrectomized rats
1 Insitute of Pathology 2 Department of Internal Medicine, University of Heidelberg, Heidelberg, Germany 3 Department of Nephrology, Endocrinology and Metabolic Diseases Medical University of Silesia, Katowice, Poland
Correspondence and offprint requests to: Nadezda Koleganova, Department of Pathology, University of Heidelberg, Im Neuenheimer Feld 220/221, D-69120 Heidelberg, Germany. Tel: +49-6221-5639917; Fax: +49-6221-565251; E-mail: nad_ko{at}gmx.de
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Abstract |
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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-β1, 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-β1 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.
Keywords: calcitriol; cardiac remodelling; chronic renal failure; secondary hyperparathyroidism; vitamin D
Received for publication: 7. 5.08
Accepted in revised form: 8. 9.08
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