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- Title
T-type calcium channel blockade as a therapeutic strategy against renal injury in rats with subtotal nephrectomy.
- Authors
Sugano, N.; Wakino, S.; Kanda, T.; Tatematsu, S; Homma, K.; Yoshioka, K.; Hasegawa, K.; Hara, Y.; Suetsugu, Y.; Yoshizawa, T.; Utsunomiya, Y.; Tokudome, G.; Hosoya, T.; Saruta, T.; Hayashi, K.
- 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.Kidney International (2008) 73, 826–834; doi:10.1038/sj.ki.5002793; published online 16 January 2008
- Subjects
HYPERTENSION; KIDNEY diseases; CALCIUM channels; PROTEINURIA; HEMODYNAMICS; LABORATORY rats
- Publication
Kidney International, 2008, Vol 73, Issue 7, p826
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1038/sj.ki.5002793