Prevention of aortic calcification by etidronate in the renal failure rat model.
Our recent clinical study indicated that etidronate may inhibit the progression of aortic calcification in hemodialysis patients. To determine whether etidronate inhibits aortic calcification in renal failure rats, renal failure was induced by subtotal nephrectomy, in which 5/6 of the kidneys were removed. Significant increases in serum creatinine levels were observed 2 weeks after the operation, at which point treatment with etidronate and calcitriol was initiated. Etidronate at 5 or 10 mg/kg significantly reduced the thoracic and abdominal aortic calcification induced by calcitriol. It also reduced the dysfunction in aortic contraction. The elevation of bone metabolism and reduction of bone mineral density observed in the nephrectomized rats were not affected by treatment with 5 mg/kg etidronate. No changes in serum Ca and the product of Ca and P levels were observed between the non etidronate-treated group and the 5 mg/kg etidronate-treated group. Moreover, the reduction in the aortic expression of matrix Gla protein mRNA observed in nephrectomized rats was reversed by 5 mg/kg etidronate. These results show that etidronate at concentrations that do not affect the bone mineral density inhibits aortic calcification and recovers vascular dysfunction in renal failure rats.
Tamura
Kazuhiro
K
Department of Endocrine Pharmacology, Tokyo University of Pharmacy and Life Science, Horinouchi 1432-1, Hachioji, Tokyo, Japan. hiro@ps.toyaku.ac.jp
Suzuki
Yusuke
Y
Matsushita
Mayumi
M
Fujii
Hiroyuki
H
Miyaura
Chisato
C
Aizawa
Sumio
S
Kogo
Hiroshi
H
D000818:Animals; D001018:Aortic Diseases / Q000517:prevention & control*; D015519:Bone Density / Q000187:drug effects; D002114:Calcinosis / Q000517:prevention & control*; D002118:Calcium / Q000097:blood; D002135:Calcium-Binding Proteins / Q000235:genetics; D004195:Disease Models, Animal; D012968:Etidronic Acid / Q000627:therapeutic use*; D016326:Extracellular Matrix Proteins / Q000235:genetics; D008297:Male; D009392:Nephrectomy; D053495:Osteopontin / Q000235:genetics; D010281:Parathyroid Hormone / Q000097:blood; D010758:Phosphorus / Q000097:blood; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D051437:Renal Insufficiency / Q000150:complications*; D014661:Vasoconstriction / Q000187:drug effects; D000097568:Matrix Gla Protein
D002118:Calcium; D002135:Calcium-Binding Proteins; D012968:Etidronic Acid; D016326:Extracellular Matrix Proteins; D053495:Osteopontin; D010281:Parathyroid Hormone; D010758:Phosphorus; D012333:RNA, Messenger; D000097568:Matrix Gla Protein