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Cytosolic calcium and lymphoproliferative response during calcium antagonism in men
1Department of Molecular and Cardiovascular Research, KU Leuven, Belgium. paul.lijnen@med.kuleuven.ac.be
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.
Insights
Mibefradil, a calcium channel blocker, effectively lowers blood pressure in men. This action is linked to reduced intracellular free calcium and decreased DNA synthesis in peripheral blood mononuclear cells (PBMC).
Area of Science:
- Pharmacology
- Cardiovascular Medicine
- Cell Biology
Background:
- Mibefradil is a novel calcium channel blocker with selective T-type channel activity.
- Understanding its effects on cardiovascular parameters and cellular processes is crucial.
Purpose of the Study:
- To investigate the effects of mibefradil on blood pressure, intracellular cation concentrations, sodium-proton exchange, and DNA synthesis in peripheral blood mononuclear cells (PBMC).
Main Methods:
- A double-blind, placebo-controlled study involving 40 male subjects over 2 weeks.
- Subjects received either placebo or 50 mg mibefradil daily.
- Measurements included blood pressure, heart rate, intracellular ion concentrations, sodium-proton exchange rate, and 3H-thymidine incorporation in PBMC.
Main Results:
- Mibefradil significantly reduced standing and recumbent blood pressure and heart rate compared to placebo.
- Intracellular free calcium concentration and 3H-thymidine incorporation in PBMC were significantly decreased.
- No significant changes were observed in intracellular sodium, potassium, magnesium concentrations, or sodium-proton exchange rate.
Conclusions:
- Mibefradil effectively lowers blood pressure in men, associated with reduced intracellular free calcium.
- The drug also inhibits de novo DNA synthesis in PBMC, likely by modulating calcium homeostasis.