Cytosolic calcium and lymphoproliferative response during calcium antagonism in men

Objective: A double-blind, placebo-controlled parallel study was conducted on the effect of mibefradil, both an L- and T-type Ca²⁺-channel blocker with a more selective blockade of T-type channels, administered once daily for 1 week to normal male subjects, on blood pressure, intracellular cationic concentrations, sodium-proton exchange rate and ³ H-thymidine incorporation in peripheral blood mononuclear cells (PBMC). Methods: After a 1-week run-in period on placebo, the subjects (n = 40) were allocated to a placebo or a mibefradil group. Placebo or 50 mg mibefradil was administered once daily in the morning for 1 week. All subjects were investigated at baseline and after 1 week of placebo or mibefradil administration. Standing or recumbent blood pressure and heart rate of subjects in the mibefradil group was decreased (P < 0.05 or less) compared with that of subjects in the placebo group. Results: Decreased (P < 0.001) intracellular free Ca²⁺ concentration and reduced (P < 0.001) ³ H-thymidine incorporation in the PBMC were observed in the mibefradil-treated subjects. The intracellular sodium, potassium or magnesium concentration as well as the sodium-proton exchange rate were not changed during mibefradil administration. Conclusion: The blood pressure lowering action of mibefradil in men is accompanied by a decrease in intracellular free Ca²⁺ concentration. Mibefradil also reduced the ³ H-thymidine incorporation or de novo DNA synthesis in PBMC by modulating the calcium homeostasis. Received: 24 June 1998 / Accepted in revised form: 3 October 1998