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NDT Advance Access originally published online on July 12, 2006
Nephrology Dialysis Transplantation 2006 21(10):2754-2761; doi:10.1093/ndt/gfl270
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© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

High-calcium vs high-phosphate intake and small artery tone in advanced experimental renal insufficiency

Peeter Kööbi1,2, Tuija I. Vehmas1, Pasi Jolma1,3, Jarkko Kalliovalkama1,4, Meng Fan1, Onni Niemelä5, Heikki Saha6,7, Mika Kähönen8, Pauli Ylitalo1, Jaana Rysä9, Heikki Ruskoaho9 and Ilkka Pörsti6,7,

1Department of Pharmacological Sciences, University of Tampere, Tampere, 2Department of Ophthalmology, Satakunta Central Hospital, Pori, 3Department of Neurology, Tampere University Hospital, Tampere, 4Coxa Hospital for Joint Replacement, Tampere, 5Seinäjoki Central Hospital Laboratory, Department of Clinical Chemistry, Seinäjoki, 6Internal Medicine, University of Tampere, Tampere, 7Internal Medicine, 8Clinical Physiology, Tampere University Hospital, Tampere and 9Department of Pharmacology and Toxicology, Biocenter Oulu, University of Oulu, Oulu, Finland

Correspondence and offprint requests to: Ilkka Pörsti, MD, Medical School, Department of Internal Medicine, FIN-33014, University of Tampere, Finland. Email: ilkka.porsti{at}uta.fi

Background. Disturbed calcium–phosphorus balance significantly contributes to uraemic changes in large arteries. We examined the influences of high-calcium and high-phosphate intake on small artery tone in experimental renal insufficiency.

Methods. Sixty-five rats were assigned to 5/6 nephrectomy (NTX) or sham operation. After 15 week disease progression, NTX rats were given high-calcium (3%), high-phosphate (1.5%) or control diet (0.3% calcium, 0.5% phosphate) for 12 weeks. Then isolated segments of small mesenteric arteries were studied using wire and pressure myographs.

Results. Subtotal nephrectomy reduced creatinine clearance by 60% and increased parathyroid hormone (PTH) and phosphate 12-fold and 2.7-fold, respectively. High-phosphate intake further elevated PTH and phosphate (33-fold and 5.5-fold, respectively), while the calcium diet suppressed them (to 3.5 and 62% vs sham, respectively). Ventricular B-type natriuretic peptide synthesis was increased, and blood pressure was 27 and 18 mmHg higher in NTX rats on control and phosphate diet, respectively, than in calcium-fed rats. Vasorelaxation to acetylcholine was impaired by ~50% in uraemic rats, and was further deteriorated by high-phosphate intake, whereas the calcium diet improved endothelium-mediated relaxation via nitric oxide and potassium channels. Small arteries of all NTX groups featured eutrophic inward remodelling: wall-to-lumen ratio was increased 1.3-fold without change in cross-sectional area.

Conclusion. High-phosphate intake had a detrimental influence on secondary hyperparathyroidism and vasodilatation, whereas high-calcium intake reduced blood pressure and PTH, alleviated volume overload and improved vasorelaxation in experimental renal insufficiency. Therefore, alterations in the calcium–phosphorus balance can significantly modulate small artery tone during impaired kidney function.

Keywords: arterial function; calcium; endothelium; kidney failure chronic; phosphate; PTH


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