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Nephron Exp Nephrol. 2008;109(3):e84-93. doi: 10.1159/000145464. Epub 2008 Jul 25.

Paricalcitol treatment and arterial tone in experimental renal insufficiency.

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1
Medical School, University of Tampere, Tampere, Finland.

Abstract

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.

PMID:
18663335
DOI:
10.1159/000145464
[Indexed for MEDLINE]
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