Effect of calcium channel blockers, nifedipine and benidipine, on death ofcultured mouse mesangial cells

We examined the effects of the short-acting calcium channel blocker (CCB) n ifedipine 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 usin g semithin sections. The dead cells were divided into three types, i.e., ap optotic cells (type 1), necrotic cells (type 3) and other types of dead cel ls, the so-called 'secondary necrotic cells' or 'postapoptotic necrotic cel ls' (type 2), In the morphological study with semithin sections, cells in t he presence of TNF-alpha or CHX and nifedipine or benidipine showed low per centages of all dead cell types with 24 h incubation. Both nifedipine and b enidipine have protective effects against TNF-alpha or CHX. It is postulate d that CCB might inhibit the apoptotic or necrotic processes by TNF-alpha o r CHX with 24 h incubation. With 36 h incubation, CCB increased the percent ages of all types of dead cells except for treatment with 1x10(-5) M benidi pine and CHX. It appears that these cell-protective effects might be decrea sed 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 pro tective 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. Copyright (C) 2000 S. Karger A G, Basel.