The Effect of Verapamil and Diltiazem on Alveolar Type II Cells during Warm and Cold Metabolic Ischaemia

Abstract

The alteration of cytosolic free calcium concentration is an important event during cellular ischaemia. Calcium channel blockers have been shown to be beneficial during experimental ischaemic organ protection. To investigate the mechanisms of this protection, the behaviour of type II pneumocyte cultures, subjected to warm and cold metabolic ischaemia (6 h), was studied. The cells were incubated in electrolytic solutions and treated with high doses of verapamil (10 mg/l) or diltiazem (100 mg/l). Alveolar type II epithelial cells were removed from adult rat lungs using the modified Dobbs' method. Cell viability was determined by analysis of the total protein content, and from the rate of protein synthesis as indicated by the [35S]methionine uptake assay. The results show that verapamil does not have a direct cytoprotective or cytotoxic effect on the incubated cells, but diltiazem seems to be toxic to the cells, especially during cold ischaemia when the toxicity is significant ( P < 0.05). Thus, the protection from ischaemia previously attributed to calcium channel blockers is ascribed to action on the blood vessels resulting in vasodilatation, rather than to a direct influence on cytosolic free calcium homeostasis.