Effect of Calcium Channel Blockers, Nifedipine and Benidipine, on Death of Cultured Mouse Mesangi al Cells

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–α) 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–α 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–α or CHX. It is postulated that CCB might inhibit the apoptotic or necrotic processes by TNF–α or CHX with 24 h incubation. With 36 h incubation, CCB increased the percentages of all types of dead cells except for treatment with 1×10^–5 M benidipine and CHX. It appears that these cell–protective effects might be decreased after treatment with TNF–α 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–α or CHX . However, nifedipine and benidipine did not inhibit specific types of cell death using semithin sections in this study.