Effect of calcium channel blockers, nifedipine and benidipine, on death of cultured mouse mesangi al cells

Kidney Blood Press Res. 2000;23(2):126-32. doi: 10.1159/000025965.

Abstract

We examined the effects of the short-acting calcium channel blocker (CCB) nifedipine and the long-acting CCB benidipine on the death of mouse cultured mesangial cells induced by tumor necrosis factor alpha (TNF-alpha) and/or cycloheximide (CHX). Cell death was evaluated by a morphological study using semithin sections. The dead cells were divided into three types, i.e., apoptotic cells (type 1), necrotic cells (type 3) and other types of dead cells, the so-called 'secondary necrotic cells' or 'postapoptotic necrotic cells' (type 2). In the morphological study with semithin sections, cells in the presence of TNF-alpha or CHX and nifedipine or benidipine showed low percentages of all dead cell types with 24 h incubation. Both nifedipine and benidipine have protective effects against TNF-alpha or CHX. It is postulated that CCB might inhibit the apoptotic or necrotic processes by TNF-alpha or CHX with 24 h incubation. With 36 h incubation, CCB increased the percentages of all types of dead cells except for treatment with 1x10(-5) M benidipine and CHX. It appears that these cell-protective effects might be decreased after treatment with TNF-alpha or CHX and CCB for 36 h. In conclusion, the short-acting CCB nifedipine and the long-acting CCB benidipine have protective effects on mouse cultured mesangial cells against TNF-alpha or CHX. However, nifedipine and benidipine did not inhibit specific types of cell death using semithin sections in this study.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Calcium Channel Blockers / pharmacology*
  • Cell Death / drug effects
  • Cells, Cultured
  • Cycloheximide / pharmacology
  • Dihydropyridines / pharmacology*
  • Glomerular Mesangium / chemistry*
  • Glomerular Mesangium / drug effects
  • Glomerular Mesangium / enzymology
  • L-Lactate Dehydrogenase / metabolism
  • Mice
  • Nifedipine / pharmacology*
  • Protein Synthesis Inhibitors / pharmacology
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Calcium Channel Blockers
  • Dihydropyridines
  • Protein Synthesis Inhibitors
  • Tumor Necrosis Factor-alpha
  • benidipine
  • Cycloheximide
  • L-Lactate Dehydrogenase
  • Nifedipine