Paricalcitol treatment and arterial tone in experimental renal insufficiency.
OBJECTIVE
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.


CONCLUSIONS
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.
Karavalakis
Emmanouil
E
Medical School, University of Tampere, Tampere, Finland.
Eräranta
Arttu
A
Vehmas
Tuija I
TI
Koskela
Jenni K
JK
Kööbi
Peeter
P
Mustonen
Jukka
J
Niemelä
Onni
O
Rysä
Jaana
J
Ruskoaho
Heikki
H
Pörsti
Ilkka
I
D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D004872:Ergocalciferols / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D051437:Renal Insufficiency / Q000188:drug therapy* / Q000503:physiopathology
D004872:Ergocalciferols; C084656:paricalcitol