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

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 alpha-smooth muscle actin and vimentin along with transforming growth factor-beta (TGF-beta)-induced renal Rho-kinase activity seen in the control group. Subtotal nephrectomy enhanced renal T-type calcium channel alpha1G subunit expression mimicked in angiotensin II-stimulated mesangial cells or TGF-beta-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.

• Authors: 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
• Journal: Kidney international (Kidney Int) Vol. 73 Issue 7 Pg. 826-34 (Apr 2008) ISSN: 1523-1755 [Electronic] United States
• PMID: 18200001 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calcium Channel Blockers
• Calcium Channels, T-Type
• Dihydropyridines
• Nitrophenols
• Organophosphorus Compounds
• efonidipine

Topics

• Animals
• Calcium Channel Blockers (therapeutic use)
• Calcium Channels, T-Type (drug effects)
• Chronic Disease
• Dihydropyridines (therapeutic use)
• Hypertension (complications, drug therapy)
• Kidney Diseases (etiology, prevention & control)
• Male
• Nephrectomy (methods)
• Nitrophenols (therapeutic use)
• Organophosphorus Compounds (therapeutic use)
• Rats
• Rats, Inbred SHR