Spironolactone ameliorates arterial medial calcification in uremic rats: The role of mineralocorticoid receptor signaling in vascular calcification

Narihito Tatsumoto, Shunsuke Yamada, Masanori Tokumoto, Masahiro Eriguchi, Hideko Noguchi, Kumiko Torisu, Kazuhiko Tsuruya, Takanari Kitazono

研究成果: ジャーナルへの寄稿記事

16 引用 (Scopus)

抄録

Vascular calcification (VC) is a critical complication in patients with chronic kidney disease (CKD). The effects of spironolactone (SPL), a mineralocorticoid receptor (MR) antagonist, on VC have not been fully investigated in CKD. The present in vivo study determined the protective effects of SPL on VC in CKD rats. Rats were divided into a control group and four groups of rats with adenine-induced CKD. Three groups were treated with 0, 50, and 100 mg·kg-1·day-1 SPL for 8 wk, and one group was treated with 100 mg·kg-1·day-1 SPL for the last 2 wk of the 8-wk treatment period. After 8 wk, CKD rats developed azotemia and hyperphosphatemia, with increases in the expression of serum and glucocorticoid-regulated kinase-1 and sodium-phosphate cotransporter, in inflammation and oxidative stress level, in osteogenic signaling and apoptosis, and in aortic calcification, compared with control rats. SPL dose dependently decreased these changes in the aortas, concomitant with improvements in renal inflammation, tubulointerstitial nephritis, and kidney function. SPL neither lowered blood pressure level nor induced hyperkalemia. Treatment of CKD rats for the last 2 wk with 100 mg·kg-1·day-1 SPL attenuated VC compared with CKD rats with the same degree of kidney function and hyperphosphatemia. In conclusion, SPL dose dependently inhibits the progression of VC by suppressing MR signaling, local inflammation, osteogenic transition, and apoptosis in the aortas of CKD rats.

元の言語英語
ページ(範囲)F967-F979
ジャーナルAmerican Journal of Physiology - Renal Physiology
309
発行部数11
DOI
出版物ステータス出版済み - 1 1 2015

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Vascular Calcification
Mineralocorticoid Receptors
Spironolactone
Chronic Renal Insufficiency
Hyperphosphatemia
Inflammation
Kidney
Aorta
Sodium-Phosphate Cotransporter Proteins
Apoptosis
Mineralocorticoid Receptor Antagonists
Azotemia
Interstitial Nephritis
Hyperkalemia
Adenine
Oxidative Stress
Blood Pressure
Control Groups

All Science Journal Classification (ASJC) codes

  • Physiology
  • Urology

これを引用

Spironolactone ameliorates arterial medial calcification in uremic rats : The role of mineralocorticoid receptor signaling in vascular calcification. / Tatsumoto, Narihito; Yamada, Shunsuke; Tokumoto, Masanori; Eriguchi, Masahiro; Noguchi, Hideko; Torisu, Kumiko; Tsuruya, Kazuhiko; Kitazono, Takanari.

:: American Journal of Physiology - Renal Physiology, 巻 309, 番号 11, 01.01.2015, p. F967-F979.

研究成果: ジャーナルへの寄稿記事

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abstract = "Vascular calcification (VC) is a critical complication in patients with chronic kidney disease (CKD). The effects of spironolactone (SPL), a mineralocorticoid receptor (MR) antagonist, on VC have not been fully investigated in CKD. The present in vivo study determined the protective effects of SPL on VC in CKD rats. Rats were divided into a control group and four groups of rats with adenine-induced CKD. Three groups were treated with 0, 50, and 100 mg·kg-1·day-1 SPL for 8 wk, and one group was treated with 100 mg·kg-1·day-1 SPL for the last 2 wk of the 8-wk treatment period. After 8 wk, CKD rats developed azotemia and hyperphosphatemia, with increases in the expression of serum and glucocorticoid-regulated kinase-1 and sodium-phosphate cotransporter, in inflammation and oxidative stress level, in osteogenic signaling and apoptosis, and in aortic calcification, compared with control rats. SPL dose dependently decreased these changes in the aortas, concomitant with improvements in renal inflammation, tubulointerstitial nephritis, and kidney function. SPL neither lowered blood pressure level nor induced hyperkalemia. Treatment of CKD rats for the last 2 wk with 100 mg·kg-1·day-1 SPL attenuated VC compared with CKD rats with the same degree of kidney function and hyperphosphatemia. In conclusion, SPL dose dependently inhibits the progression of VC by suppressing MR signaling, local inflammation, osteogenic transition, and apoptosis in the aortas of CKD rats.",
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AU - Yamada, Shunsuke

AU - Tokumoto, Masanori

AU - Eriguchi, Masahiro

AU - Noguchi, Hideko

AU - Torisu, Kumiko

AU - Tsuruya, Kazuhiko

AU - Kitazono, Takanari

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