Systemic cardiovascular disease in uremic rats induced by 1,25(OH)2D3.
OBJECTIVE
Vitamin D may contribute to cardiovascular disease in the absence of hypercalcemia in patients with chronic kidney disease.


METHODS
We investigated the effects of long-term (6-week) treatment with 1,25(OH)2D3, at a non-hypercalcemic dosage (0.25 microg/kg per day per orally) in 5/6 nephrectomized rats: (i) vehicle-treated, sham-operated rats; (ii) 1,25(OH)2D3-treated, sham-operated rats; (iii) vehicle-treated, 5/6 nephrectomized rats; and (iv) 1,25(OH)2D3-treated, 5/6 nephrectomized rats.


RESULTS
Creatinine clearance after 6 weeks was significantly lower and parathyroid hormone levels were significantly higher in 1,25(OH)2D3-treated uremic rats, compared with uremic controls (P < 0.01). Serum calcium levels, as well as the calcium-phosphorus product, did not differ between both groups. Mean systolic blood pressure in 1,25(OH)2D3-treated animals was significantly increased, compared with vehicle (each P < 0.01). In addition, 1,25(OH)2D3-treated uremic animals showed left ventricular hypertrophy. Diffuse aortic calcification involving the intima and media layer occurred in 1,25(OH)2D3-treated uremic animals, but not in other groups. The mean aortic wall area and lumen area were increased two-fold in 1,25(OH)2D3-treated uremic animals compared with vehicle (P < 0.01), whereas the wall/lumen ratio remained unchanged, indicating fusiform aneurysm formation.


CONCLUSIONS
Hypertension, left ventricular hypertrophy, aortic calcification, and aneurysm, without hypercalcemia, occurred in 1,25(OH)2D3-treated, 5/6 nephrectomized rats. These data indicate a permissive effect of uremia for cardiovascular damage induced by non-hypercalcemic doses of 1,25(OH)2D3.
Haffner
Dieter
D
Center for Cardiovascular Research, Charité Hospital, Humboldt University at Berlin, Germany. dieter.haffner@charite.de
Hocher
Berthold
B
Müller
Dominik
D
Simon
Katja
K
König
Kai
K
Richter
Claus-Michael
CM
Eggert
Barbara
B
Schwarz
Johanna
J
Godes
Michael
M
Nissel
Richard
R
Querfeld
Uwe
U
D000783:Aneurysm / Q000139:chemically induced; D000818:Animals; D001018:Aortic Diseases / Q000139:chemically induced; D002114:Calcinosis / Q000139:chemically induced; D002117:Calcitriol / Q000633:toxicity*; D002118:Calcium / Q000097:blood; D002318:Cardiovascular Diseases / Q000139:chemically induced*; D004435:Eating / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced; D017379:Hypertrophy, Left Ventricular / Q000139:chemically induced; D008297:Male; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D014511:Uremia / Q000150:complications*
D010281:Parathyroid Hormone; D010710:Phosphates; D002117:Calcitriol; D002118:Calcium