T-type calcium channel blockade as a therapeutic strategy against renal injury in rats with subtotal nephrectomy

N. Sugano, S. Wakino, T. Kanda, S. Tatematsu, K. Homma, K. Yoshioka, K. Hasegawa, Y. Hara, Y. Suetsugu, T. Yoshizawa, Y. Hara, Y. Utsunomiya, G. Tokudome, T. Hosoya, T. Saruta, K. Hayashi

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Abstract

T-type calcium channel blockers have been previously shown to protect glomeruli from hypertension by regulating renal arteriolar tone. To examine whether blockade of these channels has a role in protection against tubulointerstitial damage, we used a stereo-selective T-type calcium channel blocker R(-)-efonidipine and studied its effect on the progression of this type of renal injury in spontaneously hypertensive rats that had undergone subtotal nephrectomy. Treatment with racemic efonidipine for 7 weeks significantly reduced systolic blood pressure and proteinuria. The R(-)-enantiomer, however, had no effect on blood pressure but significantly reduced proteinuria compared to vehicle-treated rats. Both agents blunted the increase in tubulointerstitial fibrosis, renal expression of α-smooth muscle actin and vimentin along with transforming growth factor-β (TGF-β)-induced renal Rho-kinase activity seen in the control group. Subtotal nephrectomy enhanced renal T-type calcium channel α1G subunit expression mimicked in angiotensin II-stimulated mesangial cells or TGF-β-stimulated proximal tubular cells. Our study shows that T-type calcium channel blockade has renal protective actions that depend not only on hemodynamic effects but also pertain to Rho-kinase activity, tubulointerstitial fibrosis, and epithelial-mesenchymal transitions.

Original languageEnglish
Pages (from-to)826-834
Number of pages9
JournalKidney international
Volume73
Issue number7
DOIs
Publication statusPublished - 2008 Apr

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Keywords

  • Chronic kidney disease
  • Hypertension
  • Proteinuria
  • R(-)-efonidipine
  • Renal fibrosis
  • Rho/Rho-kinase
  • T-type Ca channels

ASJC Scopus subject areas

  • Nephrology

Cite this

Sugano, N., Wakino, S., Kanda, T., Tatematsu, S., Homma, K., Yoshioka, K., Hasegawa, K., Hara, Y., Suetsugu, Y., Yoshizawa, T., Hara, Y., Utsunomiya, Y., Tokudome, G., Hosoya, T., Saruta, T., & Hayashi, K. (2008). T-type calcium channel blockade as a therapeutic strategy against renal injury in rats with subtotal nephrectomy. Kidney international, 73(7), 826-834. https://doi.org/10.1038/sj.ki.5002793