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


CONCLUSIONS
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.
Kööbi
Peeter
P
Medical School, Department of Internal Medicine, FIN-33014, University of Tampere, Finland.
Vehmas
Tuija I
TI
Jolma
Pasi
P
Kalliovalkama
Jarkko
J
Fan
Meng
M
Niemelä
Onni
O
Saha
Heikki
H
Kähönen
Mika
M
Ylitalo
Pauli
P
Rysä
Jaana
J
Ruskoaho
Heikki
H
Pörsti
Ilkka
I
D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002136:Calcium, Dietary / Q000008:administration & dosage / Q000494:pharmacology*; D003401:Creatine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004727:Endothelium / Q000378:metabolism; D006961:Hyperparathyroidism / Q000139:chemically induced / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000503:physiopathology; D009599:Nitroprusside / Q000494:pharmacology; D010281:Parathyroid Hormone / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D016226:Phosphorus, Dietary / Q000008:administration & dosage / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D051437:Renal Insufficiency / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects
D002136:Calcium, Dietary; D010281:Parathyroid Hormone; D010710:Phosphates; D016226:Phosphorus, Dietary; D009599:Nitroprusside; C046783:11,12-epoxy-5,8,14-eicosatrienoic acid; D015126:8,11,14-Eicosatrienoic Acid; D003401:Creatine; D000109:Acetylcholine; D002118:Calcium