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NDT Advance Access published online on July 12, 2006

Nephrology Dialysis Transplantation, 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
Received March 4, 2006
Accepted April 18, 2006


Original Article

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

Peeter Kööbi 1, Tuija I. Vehmas 2, Pasi Jolma 3, Jarkko Kalliovalkama 4, Meng Fan 2, Onni Niemelä 5, Heikki Saha 6, Mika Kähönen 7, Pauli Ylitalo 2, Jaana Rysä 8, Heikki Ruskoaho 8, and Ilkka Pörsti 6 *

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

* To whom correspondence should be addressed.
Ilkka Pörsti, E-mail: ilkka.porsti{at}uta.fi



  Abstract

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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