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

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19 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)F967-F979
JournalAmerican Journal of Physiology - Renal Physiology
Volume309
Issue number11
DOIs
Publication statusPublished - 2015

All Science Journal Classification (ASJC) codes

  • Physiology
  • Urology

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