Aim: To examine whether treatment of secondary hyperparathyroidism with paricalcitol provides benefits to arteries in uremic rats. Methods: 5/6-nephrectomized rats were treated (NX+Pari) or not treated (NX) with paricalcitol (200 ng/kg, thrice weekly) for 12 weeks. Aortic histology and isolated segments of the main and 2nd-order mesenteric arterial branches were studied. Results: Creatinine clearance was reduced by 54–61%, plasma phosphate increased 2.1- to 2.5-fold, and blood pressure by 40 mm Hg in both NX groups. PTH increased 13-fold in NX and 5-fold in NX+Pari rats. Calcification in aortic cross-sections increased from 2.1 to 7.1% after paricalcitol. In the large mesenteric artery, vasoconstriction to noradrenaline was reduced in NX+Pari rats. In the large and small arteries, vasorelaxation to acetylcholine was impaired in NX rats and unaffected by paricalcitol. In the small artery, paricalcitol increased nitric oxide synthase inhibition-resistant relaxation to acetylcholine, and maximal relaxation to levcromakalim. The small arteries of NX rats featured increased wall cross-sectional area, while paricalcitol further increased wall thickness and the wall:lumen ratio. Conclusion: Paricalcitol treatment showed both benefits and harmful effects in uremic rats: in the large artery vasoconstriction was reduced but calcification increased, while in the small artery vasorelaxation via potassium channels was moderately improved but hypertrophic remodeling was aggravated.

Our aim was to compare the effects of calcium carbonate and sevelamer-HCl treatments on calcium-phosphate metabolism and renal function in 5/6 nephrectomized (NX) rats so that long-term disease progression preceded the treatment. After 15-week progression, calcium carbonate (3.0%), sevelamer-HCl (3.0%), or control diets (0.3% calcium) were given for 9 weeks. Subtotal nephrectomy reduced creatinine clearance (−40%), plasma calcidiol (−25%), and calcitriol (−70%) and increased phosphate (+37%), parathyroid hormone (PTH) (11-fold), and fibroblast growth factor-23 (FGF-23) (4-fold). In NX rats, calcium carbonate diet increased plasma (+20%) and urinary calcium (6-fold), reduced plasma phosphate (−50%) and calcidiol (−30%), decreased creatinine clearance (−35%) and FGF 23 (−85%), and suppressed PTH without influencing blood pH. In NX rats, sevelamer-HCl increased urinary calcium (4-fold) and decreased creatinine clearance (−45%), PTH (−75%), blood pH (by 0.20 units), plasma calcidiol (−40%), and calcitriol (−65%). Plasma phosphate and FGF-23 were unchanged. In conclusion, when initiated after long-term progression of experimental renal insufficiency, calcium carbonate diet reduced plasma phosphate and FGF-23 while sevelamer-HCl did not. The former induced hypercalcemia, the latter induced acidosis, while both treatments reduced vitamin D metabolites and deteriorated renal function. Thus, delayed initiation influences the effects of these phosphate binders in remnant kidney rats.