Vascular calcification: contribution of parathyroid hormone in renal failure.
Hyperphosphatemia is a driving force in the pathogenesis of vascular calcification (VC) and secondary hyperparathyroidism associated with renal failure. To test for the possible contribution of parathyroid hormone (PTH) to cardiovascular calcification, we removed the parathyroid glands from rats but infused synthetic hormone at a supraphysiologic rate. All rats were pair-fed low, normal, or high phosphorus diets and subjected to a sham or 5/6 nephrectomy (remnant kidney). Control rats were given a normal diet and underwent both sham parathyroidectomy and 5/6 nephrectomy. Heart weight/body weight ratios and serum creatinine levels were higher in remnant kidney rats than in the sham-operated rats. Remnant kidney rats on the high phosphorus diet and PTH replacement developed hyperphosphatemia and hypocalcemia along with low bone trabecular volume. Remnant kidney rats on the low phosphorus diet or intact kidney rats on a normal phosphorus diet, each with hormone replacement, developed hypercalcemia. All rats on PTH replacement developed intense aortic medial calcification, and some animals presented coronary calcification. We suggest that high PTH levels induce high bone turnover and medial calcification resembling Mömckeberg's sclerosis independent of uremia. This model may be useful in defining mechanisms underlying VC.
Neves
K R
KR
Department of Internal Medicine, Nephrology Division, University of São Paulo, São Paulo, SP, Brazil.
Graciolli
F G
FG
dos Reis
L M
LM
Graciolli
R G
RG
Neves
C L
CL
Magalhães
A O
AO
Custódio
M R
MR
Batista
D G
DG
Jorgetti
V
V
Moysés
R M A
RM
D000818:Animals; D001011:Aorta / Q000473:pathology; D001835:Body Weight / Q000187:drug effects; D016723:Bone Remodeling; D002114:Calcinosis / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D002318:Cardiovascular Diseases / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D003331:Coronary Vessels / Q000473:pathology; D004195:Disease Models, Animal; D004435:Eating / Q000187:drug effects; D006934:Hypercalcemia / Q000209:etiology; D008297:Male; D010281:Parathyroid Hormone / Q000494:pharmacology / Q000502:physiology*; D010991:Plethysmography; D051381:Rats; D017208:Rats, Wistar; D051437:Renal Insufficiency / Q000209:etiology*
D010281:Parathyroid Hormone