title: Cinacalcet suppresses calcification of the aorta and heart in uremic rats.
abstract: High serum parathyroid hormone levels are associated with vascular calcification. Cinacalcet is a calcimimetic agent that inhibits parathyroid hormone secretion and is used to treat patients with secondary hyperparathyroidism. Here we measured the effects of oral cinacalcet on calcification of the aorta and heart in rats with a remnant kidney (5/6 nephrectomy) model of uremia that were fed a high-phosphate diet containing lactose to accelerate the process of aortic calcification. Alizarin red staining showed that the smooth muscle in the aortic arch of rats with a remnant kidney was calcified. The tissue levels of calcium and phosphorus in the aorta and hearts of these rats were significantly increased compared to sham-operated rats. Expression of the osteoblastic lineage genes osteocalcin, osteopontin and runt-related gene 2 were also increased in the aorta of these rats. Cinacalcet suppressed these calcification-related changes by reducing serum parathyroid hormone, calcium, phosphorus, and the calcium-phosphorus product. Parathyroidectomy also suppressed calcification in this model. We suggest that cinacalcet inhibits calcification of the aorta and heart in uremic patients with secondary hyperparathyroidism by decreasing serum parathyroid hormone levels.
authors.affiliation: Pharmacology Group, Development Research Laboratories, Research Division, Kirin Pharma Co., Ltd., Takasaki, Japan.
authors.forename: Takehisa
authors.initials: T
authors.lastname: Kawata
authors.forename: Nobuo
authors.initials: N
authors.lastname: Nagano
authors.forename: Masaki
authors.initials: M
authors.lastname: Obi
authors.forename: Sonoe
authors.initials: S
authors.lastname: Miyata
authors.forename: Chika
authors.initials: C
authors.lastname: Koyama
authors.forename: Nami
authors.initials: N
authors.lastname: Kobayashi
authors.forename: Sachiko
authors.initials: S
authors.lastname: Wakita
authors.forename: Michihito
authors.initials: M
authors.lastname: Wada
mesh_terms: D000818:Animals; D001011:Aorta / Q000473:pathology*; D002114:Calcinosis / Q000188:drug therapy* / Q000517:prevention & control; D000069449:Cinacalcet; D004195:Disease Models, Animal; D006962:Hyperparathyroidism, Secondary; D009206:Myocardium / Q000473:pathology*; D009281:Naphthalenes / Q000494:pharmacology*; D010281:Parathyroid Hormone / Q000097:blood; D051381:Rats; D014511:Uremia / Q000150:complications*
chemical_list: D009281:Naphthalenes; D010281:Parathyroid Hormone; D000069449:Cinacalcet