Author:

Keywords:

Adult, Benzimidazoles, Blood Pressure, Calcium, Calcium Channel Blockers, Cell Division, Double-Blind Method, Heart Rate, Hemodynamic Processes, Humans, Ions, Leukocytes, Mononuclear, Male, Mibefradil, Placebos, Potassium, Proton Pumps, Sodium, Tetrahydronaphthalenes, Science & Technology, Life Sciences & Biomedicine, Pharmacology & Pharmacy, calcium, mibefradil, mononuclear cells, SPONTANEOUSLY HYPERTENSIVE RATS, BLOOD MONONUCLEAR-CELLS, NA+-H+ EXCHANGER, CHANNEL, MIBEFRADIL, CA2+, PROLIFERATION, INHIBITION, PRESSURE, BLOCKADE, Hemodynamics, 1115 Pharmacology and Pharmaceutical Sciences, 3214 Pharmacology and pharmaceutical sciences

Abstract:

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 3H-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) 3H-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 3H-thymidine incorporation or de novo DNA synthesis in PBMC by modulating the calcium homeostasis.